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ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma, Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03449901
Recruitment Status : Completed
First Posted : February 28, 2018
Results First Posted : September 8, 2023
Last Update Posted : September 8, 2023
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Soft Tissue Sarcoma
Interventions Drug: pegylated arginine deiminase
Drug: Gemcitabine
Drug: Docetaxel
Procedure: Tumor biopsy
Procedure: Research blood draw
Enrollment 98
Recruitment Details  
Pre-assignment Details 1 patient was enrolled, but never initiated treatment.
Arm/Group Title Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description

Patients enrolling to Cohort 1 must be diagnosed with soft tissue sarcoma.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)

Patients enrolling to Cohort 2 must be diagnosed with osteosarcoma, Ewing's sarcoma, or small cell lung cancer.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
Period Title: Overall Study
Started 82 15
Completed 1 [1] 0
Not Completed 81 15
Reason Not Completed
Progression             57             12
Adverse Event             3             0
Death             6             2
Withdrawal by Subject             12             1
Physician Decision             1             0
Patient elected for surgical intervention             1             0
Patient off for other complicating disease             1             0
[1]
1 patient completed treatment per protocol.
Arm/Group Title Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel Total
Hide Arm/Group Description

Patients enrolling to Cohort 1 must be diagnosed with soft tissue sarcoma.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)

Patients enrolling to Cohort 2 must be diagnosed with osteosarcoma, Ewing's sarcoma, or small cell lung cancer.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
 Total of all reporting groups
Overall Number of Baseline Participants 82 15 97
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 82 participants 15 participants 97 participants
57
(16 to 86)
30
(12 to 71)
55
(12 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 15 participants 97 participants
Female
45
  54.9%
7
  46.7%
52
  53.6%
Male
37
  45.1%
8
  53.3%
45
  46.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 15 participants 97 participants
Hispanic or Latino
4
   4.9%
0
   0.0%
4
   4.1%
Not Hispanic or Latino
78
  95.1%
13
  86.7%
91
  93.8%
Unknown or Not Reported
0
   0.0%
2
  13.3%
2
   2.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 15 participants 97 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
5
   6.1%
0
   0.0%
5
   5.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   7.3%
1
   6.7%
7
   7.2%
White
71
  86.6%
11
  73.3%
82
  84.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
3
  20.0%
3
   3.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 82 participants 15 participants 97 participants
82 15 97
1.Primary Outcome
Title Progression-free Survival (PFS) (Cohort 1 Only)
Hide Description
  • PFS: defined as time on study to time patients progressed on the drug combination or death or latest follow-up if progression/death is not observed yet
  • Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time Frame Through completion of follow-up (median follow-up 494 days, full range of 5-1500 days).
Hide Outcome Measure Data
Hide Analysis Population Description
PFS was evaluated only for Cohort 1; therefore, no participants in Cohort 2 were analyzed for this outcome measure. 2 participants in Cohort 1 were not evaluable for this outcome measure.
Arm/Group Title Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description:
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
Overall Number of Participants Analyzed 80 0
Median (95% Confidence Interval)
Unit of Measure: months
5.0597
(2.9898 to 7.5238)
2.Secondary Outcome
Title Overall Survival (OS) (Cohort 1 Only)
Hide Description -OS: defined as time on study to time of death due to any reasons or latest follow-up (whichever is earlier)
Time Frame Through completion of follow-up (median follow-up 494 days, full range of 5-1500 days).
Hide Outcome Measure Data
Hide Analysis Population Description
OS was evaluated only for Cohort 1; therefore, no participants in Cohort 2 were analyzed for this outcome measure. 7 participants in Cohort 1 were not evaluable for this outcome measure.
Arm/Group Title Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description:
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
Overall Number of Participants Analyzed 75 0
Median (95% Confidence Interval)
Unit of Measure: months
18.1359
(14.0290 to 25.1011)
3.Secondary Outcome
Title Clinical Benefit Rate (CBR) (Cohort 1 Only)
Hide Description
  • CBR = proportion of patients who have experienced complete response (CR)+ partial response (PR) + stable disease (SD) lasting 24 weeks or longer
  • CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
  • PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
  • SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame Through completion of treatment (median treatment of 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
CBR was evaluated only for Cohort 1; therefore, no participants in Cohort 2 were analyzed for this outcome measure. 8 participants in Cohort 1 were not evaluable for this outcome measure.
Arm/Group Title Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description:
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
Overall Number of Participants Analyzed 74 0
Measure Type: Count of Participants
Unit of Measure: Participants
27
  36.5%
4.Secondary Outcome
Title Safety and Tolerability of Regimen as Measured by Number and Grade of Adverse Events
Hide Description -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
Time Frame From start of treatment through 30 days after completion of treatment (median treatment of 9 months + 1 month follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description:
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 750 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 900 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
Overall Number of Participants Analyzed 33 25 24 15
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1-2 anemia
11
  33.3%
9
  36.0%
12
  50.0%
9
  60.0%
Grade 3-5 anemia
19
  57.6%
11
  44.0%
12
  50.0%
4
  26.7%
Grade 3-5 febrile neutropenia
2
   6.1%
3
  12.0%
1
   4.2%
1
   6.7%
Grade 1-2 eosiniphilia
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 3-5 mitral valve disease
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 atrial fibrillation
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 atrial fibrillation
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 palpitations
2
   6.1%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 pericardial effusion
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 sinus bradycardia
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 sinus tachycardia
1
   3.0%
2
   8.0%
0
   0.0%
1
   6.7%
Grade 3-5 sinus tachycardia
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 chest pain - cardiac
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 ear pain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 vertigo
1
   3.0%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 3-5 tinnitus
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 hyperthyroidism
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 cataract
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 blurred vision
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 watering eyes
1
   3.0%
2
   8.0%
2
   8.3%
0
   0.0%
Grade 1-2 retinal tear
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 dry eye
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 abdominal distension
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 abdominal pain
3
   9.1%
1
   4.0%
2
   8.3%
1
   6.7%
Grade 3-5 abdominal pain
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 anal hemorrhage
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 anal mucositis
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 ascites
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 ascites
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 bloating
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 colitis
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 colonic hemorrhage
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 colonic perforation
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 constipation
8
  24.2%
5
  20.0%
8
  33.3%
2
  13.3%
Grade 1-2 dental caries
3
   9.1%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 dental caries
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 diarrhea
10
  30.3%
7
  28.0%
7
  29.2%
1
   6.7%
Grade 3-5 diarrhea
0
   0.0%
1
   4.0%
2
   8.3%
1
   6.7%
Grade 1-2 dry mouth
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 dyspepsia
4
  12.1%
2
   8.0%
3
  12.5%
2
  13.3%
Grade 1-2 dysphagia
1
   3.0%
1
   4.0%
0
   0.0%
1
   6.7%
Grade 1-2 fecal incontinence
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 flatulence
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 gastroesophageal reflux disease
1
   3.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 hematochezia
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 generalized GI bleed
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 tooth extraction
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 hemorrhoids
0
   0.0%
2
   8.0%
1
   4.2%
0
   0.0%
Grade 3-5 lower gastrointestinal hemorrhage
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 lip pain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 mucositis oral
6
  18.2%
5
  20.0%
3
  12.5%
2
  13.3%
Grade 1-2 nausea
13
  39.4%
8
  32.0%
14
  58.3%
2
  13.3%
Grade 1-2 oral pain
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 rectal hemorrhage
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 small intestinal obstruction
2
   6.1%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 3-5 typhlitis
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 upper gastrointestinal hemorrhage
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 vomiting
6
  18.2%
4
  16.0%
3
  12.5%
4
  26.7%
Grade 3-5 vomiting
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 chills
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 5 death NOS
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 edema face
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 edema limbs
9
  27.3%
5
  20.0%
10
  41.7%
2
  13.3%
Grade 3-5 edema limbs
1
   3.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 edema trunk
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 edema trunk
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 facial pain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 fatigue
16
  48.5%
15
  60.0%
10
  41.7%
5
  33.3%
Grade 3-5 fatigue
7
  21.2%
7
  28.0%
8
  33.3%
0
   0.0%
Grade 1-2 fever
5
  15.2%
9
  36.0%
5
  20.8%
1
   6.7%
Grade 1-2 flu-like symptoms
1
   3.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 generalized edema
5
  15.2%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 infusion related reaction
1
   3.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 injection site reaction
3
   9.1%
3
  12.0%
1
   4.2%
1
   6.7%
Grade 1-2 localized edema
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 malaise
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 non-cardiac chest pain
0
   0.0%
1
   4.0%
1
   4.2%
1
   6.7%
Grade 3-5 non-cardiac chest pain
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 pain at injection site
0
   0.0%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 pain
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 3-5 hepatic hemorrhage
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 allergic reaction
3
   9.1%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 allergic reaction
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 Celiac disease
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 bladder infection
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 bronchial infection
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 enterocolitis infectious
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 enterocolitis infectious
1
   3.0%
1
   4.0%
0
   0.0%
1
   6.7%
Grade 1-2 eye infection
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 folliculitis
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 gum infection
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 influenza A infection
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 lung infection
2
   6.1%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 lung infection
1
   3.0%
1
   4.0%
2
   8.3%
1
   6.7%
Grade 1-2 papulopustular rash
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 paronychia
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 pleural infection
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 3-5 sepsis
1
   3.0%
3
  12.0%
4
  16.7%
1
   6.7%
Grade 1-2 sinusitis
3
   9.1%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 skin infection
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 3-5 skin infection
1
   3.0%
0
   0.0%
2
   8.3%
1
   6.7%
Grade 1-2 thrush
3
   9.1%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 tooth infection
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 upper respiratory infection
2
   6.1%
5
  20.0%
4
  16.7%
0
   0.0%
Grade 3-5 upper respiratory infection
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 urinary tract infection
1
   3.0%
0
   0.0%
4
  16.7%
0
   0.0%
Grade 3-5 urinary tract infection
0
   0.0%
3
  12.0%
1
   4.2%
0
   0.0%
Grade 3-5 wound infection
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 ankle fracture
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 bruising
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 fall
2
   6.1%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 3-5 fall
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 fracture
2
   6.1%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 twisted knee
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 ileal bleed due to tumor invasion
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 postoperative hemorrhage
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 spinal fracture
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 wound complication
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 activated partial thromboplastin time prolonged
1
   3.0%
2
   8.0%
3
  12.5%
0
   0.0%
Grade 3-5 activated partial thromboplastin time prolonged
1
   3.0%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 1-2 alanine aminotransferase increased
12
  36.4%
13
  52.0%
8
  33.3%
4
  26.7%
Grade 3-5 alanine aminotransferase increased
2
   6.1%
1
   4.0%
3
  12.5%
0
   0.0%
Grade 1-2 alkaline phosphatase increased
12
  36.4%
11
  44.0%
13
  54.2%
5
  33.3%
Grade 3-5 alkaline phosphatase increased
1
   3.0%
1
   4.0%
0
   0.0%
1
   6.7%
Grade 1-2 aspartate aminotransferase increased
1
   3.0%
7
  28.0%
8
  33.3%
2
  13.3%
Grade 3-5 aspartate aminotransferase increased
0
   0.0%
1
   4.0%
2
   8.3%
0
   0.0%
Grade 1-2 blood bilirubin increased
2
   6.1%
6
  24.0%
6
  25.0%
1
   6.7%
Grade 3-5 blood bilirubin increased
0
   0.0%
0
   0.0%
1
   4.2%
1
   6.7%
Grade 1-2 lactate dehydrogenase increased
2
   6.1%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 cardiac troponin I increased
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 cardiac troponin I increased
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 cardiac troponin T increased
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 creatinine increased
6
  18.2%
5
  20.0%
9
  37.5%
0
   0.0%
Grade 3-5 creatinine increased
1
   3.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 electrocardiogram QT corrected interval prolonged
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 electrocardiogram QT corrected interval prolonged
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 INR increased
4
  12.1%
3
  12.0%
9
  37.5%
0
   0.0%
Grade 3-5 GGT increased
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 3-5 INR increased
0
   0.0%
1
   4.0%
3
  12.5%
0
   0.0%
Grade 3-5 ammonia increased
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 lipase increased
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 lipase increased
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 lymphocyte count decreased
6
  18.2%
7
  28.0%
4
  16.7%
2
  13.3%
Grade 3-5 lymphocyte count decreased
18
  54.5%
11
  44.0%
20
  83.3%
8
  53.3%
Grade 1-2 neutrophil count decreased
6
  18.2%
1
   4.0%
6
  25.0%
3
  20.0%
Grade 3-5 neutrophil count decreased
19
  57.6%
18
  72.0%
11
  45.8%
7
  46.7%
Grade 1-2 platelet count decreased
6
  18.2%
5
  20.0%
9
  37.5%
4
  26.7%
Grade 3-5 platelet count decreased
23
  69.7%
18
  72.0%
12
  50.0%
7
  46.7%
Grade 1-2 weight loss
0
   0.0%
3
  12.0%
0
   0.0%
2
  13.3%
Grade 1-2 white blood cell count decreased
6
  18.2%
5
  20.0%
5
  20.8%
2
  13.3%
Grade 3-5 white blood cell count decreased
19
  57.6%
17
  68.0%
15
  62.5%
9
  60.0%
Grade 3-5 acidosis
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 anorexia
5
  15.2%
5
  20.0%
5
  20.8%
2
  13.3%
Grade 3-5 anorexia
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 dehydration
1
   3.0%
4
  16.0%
1
   4.2%
0
   0.0%
Grade 3-5 dehydration
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 hypercalcemia
1
   3.0%
2
   8.0%
1
   4.2%
1
   6.7%
Grade 1-2 hyperglycemia
6
  18.2%
4
  16.0%
5
  20.8%
2
  13.3%
Grade 3-5 hyperglycemia
0
   0.0%
1
   4.0%
2
   8.3%
0
   0.0%
Grade 1-2 hyperkalemia
1
   3.0%
1
   4.0%
0
   0.0%
2
  13.3%
Grade 3-5 hyperkalemia
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 hyperlipidemia
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 hypermagnesemia
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 hypermagnesemia
0
   0.0%
0
   0.0%
1
   4.2%
1
   6.7%
Grade 1-2 hypernatremia
1
   3.0%
1
   4.0%
1
   4.2%
1
   6.7%
Grade 1-2 hyperuricemia
6
  18.2%
5
  20.0%
6
  25.0%
2
  13.3%
Grade 3-5 hyperuricemia
2
   6.1%
0
   0.0%
4
  16.7%
0
   0.0%
Grade 1-2 hypoalbuminemia
14
  42.4%
6
  24.0%
13
  54.2%
1
   6.7%
Grade 3-5 hypoalbuminemia
1
   3.0%
2
   8.0%
2
   8.3%
2
  13.3%
Grade 1-2 hypocalcemia
12
  36.4%
6
  24.0%
11
  45.8%
2
  13.3%
Grade 3-5 hypocalcemia
3
   9.1%
1
   4.0%
1
   4.2%
2
  13.3%
Grade 1-2 hypoglycemia
1
   3.0%
1
   4.0%
2
   8.3%
0
   0.0%
Grade 3-5 hypoglycemia
0
   0.0%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 1-2 hypokalemia
5
  15.2%
6
  24.0%
7
  29.2%
2
  13.3%
Grade 3-5 hypokalemia
2
   6.1%
1
   4.0%
3
  12.5%
1
   6.7%
Grade 1-2 hyponatremia
14
  42.4%
7
  28.0%
11
  45.8%
5
  33.3%
Grade 3-5 hyponatremia
0
   0.0%
0
   0.0%
1
   4.2%
1
   6.7%
Grade 1-2 hypophosphatemia
6
  18.2%
1
   4.0%
4
  16.7%
3
  20.0%
Grade 3-5 hypophosphatemia
0
   0.0%
3
  12.0%
2
   8.3%
0
   0.0%
Grade 1-2 arthralgia
3
   9.1%
3
  12.0%
2
   8.3%
0
   0.0%
Grade 1-2 back pain
4
  12.1%
3
  12.0%
4
  16.7%
0
   0.0%
Grade 3-5 back pain
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 bone pain
3
   9.1%
2
   8.0%
3
  12.5%
2
  13.3%
Grade 1-2 flank pain
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 generalized muscle weakness
4
  12.1%
3
  12.0%
4
  16.7%
1
   6.7%
Grade 1-2 joint effusion
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 muscle cramp
6
  18.2%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 muscle weakness lower limb
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 myalgia
5
  15.2%
7
  28.0%
2
   8.3%
1
   6.7%
Grade 1-2 neck pain
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 pain in extremity
3
   9.1%
2
   8.0%
1
   4.2%
1
   6.7%
Grade 1-2 palpable lump RUE
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 skin pailloma, R hallux
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 disease progression
2
   6.1%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 1-2 tumor pain
9
  27.3%
3
  12.0%
0
   0.0%
1
   6.7%
Grade 3-5 tumor pain
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 concentration impairment
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 dizziness
1
   3.0%
5
  20.0%
2
   8.3%
0
   0.0%
Grade 1-2 dysgeusia
8
  24.2%
5
  20.0%
8
  33.3%
0
   0.0%
Grade 1-2 extrapyramidal disorder
1
   3.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 headache
5
  15.2%
5
  20.0%
3
  12.5%
1
   6.7%
Grade 1-2 plantar sensitivity
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 cerebral hemorrhage
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 neuralgia
1
   3.0%
1
   4.0%
2
   8.3%
0
   0.0%
Grade 1-2 paresthesia
2
   6.1%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 paresthesia (face)
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 peripheral sensory neuropathy
9
  27.3%
5
  20.0%
10
  41.7%
0
   0.0%
Grade 1-2 phantom pain
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 presyncope
2
   6.1%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 3-5 spinal cord compression
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 syncope
2
   6.1%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 tremor
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 3-5 agitation
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 anxiety
3
   9.1%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 confusion
2
   6.1%
2
   8.0%
0
   0.0%
1
   6.7%
Grade 3-5 confusion
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 depression
4
  12.1%
1
   4.0%
0
   0.0%
1
   6.7%
Grade 3-5 depression
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 insomnia
2
   6.1%
3
  12.0%
2
   8.3%
1
   6.7%
Grade 1-2 irritability
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 acute kidney injury
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 acute kidney injury
2
   6.1%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 dysuria
1
   3.0%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 hematuria
9
  27.3%
3
  12.0%
8
  33.3%
0
   0.0%
Grade 1-2 proteinuria
7
  21.2%
7
  28.0%
7
  29.2%
0
   0.0%
Grade 1-2 renal calculi
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 urinary frequency
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 urinary incontinence
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 urinary retention
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 urinary tract obstruction
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 genital edema
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 pelvic pain
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 groin pain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 vaginal hemorrhage
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 allergic rhinitis
1
   3.0%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 3-5 bronchial obstruction
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 cough
5
  15.2%
6
  24.0%
5
  20.8%
2
  13.3%
Grade 1-2 dyspnea
12
  36.4%
4
  16.0%
6
  25.0%
3
  20.0%
Grade 3-5 dyspnea
3
   9.1%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 epistaxis
6
  18.2%
6
  24.0%
3
  12.5%
3
  20.0%
Grade 1-2 hoarseness
1
   3.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 hypoxia
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 hypoxia
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 laryngeal hemorrhage
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 laryngeal inflammation
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 nasal congestion
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 pleural effusion
3
   9.1%
1
   4.0%
2
   8.3%
2
  13.3%
Grade 3-5 pleural effusion
2
   6.1%
0
   0.0%
1
   4.2%
1
   6.7%
Grade 3-5 pneumonitis
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 pneumothorax
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 3-5 pneumothorax
0
   0.0%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 1-2 postnasal drip
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 productive cough
2
   6.1%
2
   8.0%
1
   4.2%
0
   0.0%
Grade 3-5 pulmonary edema
1
   3.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 respiratory failure
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 chest pressure with exertion
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 rhinorrhea
2
   6.1%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 1-2 sore throat
1
   3.0%
3
  12.0%
1
   4.2%
1
   6.7%
Grade 1-2 wheezing
1
   3.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 alopecia
2
   6.1%
2
   8.0%
1
   4.2%
1
   6.7%
Grade 1-2 bullous dermatitis
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 dry skin
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 hyperhidrosis
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 nail changes
0
   0.0%
1
   4.0%
4
  16.7%
0
   0.0%
Grade 1-2 nail discoloration
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 nail loss
1
   3.0%
0
   0.0%
1
   4.2%
0
   0.0%
Grade 1-2 palmar-plantar erythrodysesthesia syndrome
0
   0.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 pruritus
1
   3.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 3-5 pruritus
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 rash acneiform
1
   3.0%
0
   0.0%
2
   8.3%
0
   0.0%
Grade 1-2 rash maculo-papular
2
   6.1%
1
   4.0%
1
   4.2%
4
  26.7%
Grade 3-5 rash maculo-papular
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 skin atrophy
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 rash NOS
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 3-5 petechial rash
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 skin ulceration
1
   3.0%
0
   0.0%
0
   0.0%
1
   6.7%
Grade 1-2 urticaria
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 minor gum transplant
2
   6.1%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 hot flashes
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 hypertension
3
   9.1%
2
   8.0%
0
   0.0%
0
   0.0%
Grade 3-5 hypertension
1
   3.0%
1
   4.0%
2
   8.3%
0
   0.0%
Grade 1-2 hypotension
1
   3.0%
3
  12.0%
3
  12.5%
0
   0.0%
Grade 3-5 hypotension
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 lymphedema
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 thromboembolic event
0
   0.0%
2
   8.0%
1
   4.2%
0
   0.0%
Grade 3-5 thromboembolic event
1
   3.0%
1
   4.0%
1
   4.2%
0
   0.0%
Grade 1-2 peripheral edema
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 muscle "tightness"
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 left hand pain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 right axillary pain
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 right neck stiffness
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 "frozen thumb"
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 hip pain
0
   0.0%
0
   0.0%
1
   4.2%
1
   6.7%
Grade 1-2 ankle sprain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 port site bleed
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 vaginal cyst
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 rash NOS on neck
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 rash NOS on bilateral UE
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 1-2 nail bed pain
1
   3.0%
0
   0.0%
0
   0.0%
0
   0.0%
Grade 1-2 feet peeling
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
Grade 3-5 leukemia secondary to oncology chemotherapy
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Number of Participants With Cancer-related Mortality (Cohort 1 Only)
Hide Description [Not Specified]
Time Frame Through completion of follow-up (median follow-up 494 days, full range of 5-1500 days).
Hide Outcome Measure Data
Hide Analysis Population Description
Cancer-related mortality was evaluated only for Cohort 1; therefore, no participants in Cohort 2 were analyzed for this outcome measure. 7 participants in Cohort 1 were not evaluable for this outcome measure.
Arm/Group Title Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description:
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
Overall Number of Participants Analyzed 75 0
Measure Type: Count of Participants
Unit of Measure: Participants
47
  62.7%
Time Frame Adverse events were collected from first dose of study treatment through 30 days after the completion of study treatment. The range of collection was 35 to 870 days, with a median following time of 87 days. All-cause mortality was collected from start of treatment through completion of follow-up. The range of collection was 5 to 1500 days, with a median follow-up time of 494 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel
Hide Arm/Group Description

Patients enrolling to Cohort 1 must be diagnosed with soft tissue sarcoma.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)

Patients enrolling to Cohort 1 must be diagnosed with soft tissue sarcoma.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 750 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)

Patients enrolling to Cohort 1 must be diagnosed with soft tissue sarcoma.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 900 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)

Patients enrolling to Cohort 2 must be diagnosed with osteosarcoma, Ewing's sarcoma, or small cell lung cancer.

  • ADI-PEG 20 will be given on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. Cycles are 21 days. ADI-PEG 20 will be given on an outpatient basis at a dose of 36 mg/m2 via intramuscular injection into either the deltoid or gluteal muscle.
  • Gemcitabine will be given intravenously at a dose of 600 mg/m2 over 90 minutes on Days 1 and 8 of each cycle. Docetaxel will be given intravenously at a dose of 60 mg/m2 over 60 minutes on Day 8 of each cycle. Patients started on gemcitabine at a dose of 900 mg/m2 or 750 mg/m2 or docetaxel at a dose of 75 mg/m2 per previous protocol version will be allowed to continue at that dose level
  • After Cycle 8, patients may continue on ADI-PEG 20 alone (without gemcitabine and docetaxel) upon request.
  • Treatment may continue for up to 34 cycles (103 weeks)
All-Cause Mortality
Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/33 (57.58%)   15/25 (60.00%)   19/24 (79.17%)   12/15 (80.00%) 
Hide Serious Adverse Events
Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/33 (42.42%)   8/25 (32.00%)   13/24 (54.17%)   5/15 (33.33%) 
Blood and lymphatic system disorders         
Anemia † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Febrile Neutropenia † 1  3/33 (9.09%)  3/25 (12.00%)  1/24 (4.17%)  1/15 (6.67%) 
Cardiac disorders         
Atrial Fibrillation † 1  0/33 (0.00%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Mitral Valve Disease † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Pericardial Effusion † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Sinus Tachycardia † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Gastrointestinal disorders         
Ascites † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Colitis † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Colonic Perforation † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Small Intestinal Obstruction † 1  2/33 (6.06%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Typhlitis † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Upper GI Hemorrhage † 1 [1]  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
General disorders         
Death NOS † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Fever † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Non-Cardiac Chest Pain † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Hepatobiliary disorders         
Hepatic Hemorrhage † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Infections and infestations         
Enterocolitis Infectious † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Lung Infection † 1  1/33 (3.03%)  1/25 (4.00%)  2/24 (8.33%)  1/15 (6.67%) 
Other † 1 [2]  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Other † 1 [3]  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Sepsis † 1  0/33 (0.00%)  3/25 (12.00%)  4/24 (16.67%)  1/15 (6.67%) 
Skin Infection † 1  1/33 (3.03%)  0/25 (0.00%)  2/24 (8.33%)  1/15 (6.67%) 
Upper Respiratory Infection † 1  2/33 (6.06%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Injury, poisoning and procedural complications         
Other † 1 [4]  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Postoperative Hemorrhage † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Spinal Fracture † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Investigations         
Neutrophil Count Decreased † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Platelet Count Decreased † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders         
Hyponatremia † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders         
Back pain † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Disease Progression † 1  1/33 (3.03%)  0/25 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Leukemia Secondary to Oncology Chemotherapy † 1 [5]  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Tumor Hemorrhage † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Tumor Pain † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Nervous system disorders         
Paresthesia † 1 [6]  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Renal and urinary disorders         
Acute Kidney Injury † 1  2/33 (6.06%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Urinary Tract Obstruction † 1  1/33 (3.03%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Bronchial Obstruction † 1 [7]  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Dyspnea † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Pleural Effusions † 1  3/33 (9.09%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Pneumonitis † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Pneumothorax † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Pulmonary Edema † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders         
Maculopapular Rash † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Vascular disorders         
Thromboembolic Event † 1  1/33 (3.03%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
1
Term from vocabulary, CTCAE (Unspecified)
†
Indicates events were collected by systematic assessment
[1]
with melena
[2]
Influenza A
[3]
COVID-19
[4]
Ileal Bleed due to tumor invasion
[5]
Due to previous Doxorubicin
[6]
Facial
[7]
due to disease progression
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/33 (100.00%)   25/25 (100.00%)   24/24 (100.00%)   15/15 (100.00%) 
Blood and lymphatic system disorders         
Anemia † 1  29/33 (87.88%)  19/25 (76.00%)  23/24 (95.83%)  13/15 (86.67%) 
Eosinophilia † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Cardiac disorders         
Atrial Fibrillation † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Chest Pain - Cardiac † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Palpitations † 1  2/33 (6.06%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Sinus Bradycardia † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Sinus Tachycardia † 1  2/33 (6.06%)  2/25 (8.00%)  0/24 (0.00%)  1/15 (6.67%) 
Ear and labyrinth disorders         
Ear Pain † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Tinnitus † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Vertigo † 1  1/33 (3.03%)  0/25 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Endocrine disorders         
Hyperthyroidism † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Eye disorders         
Blurred Vision † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Cataract † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Dry Eye † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Retinal Tear † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Watering Eyes † 1  1/33 (3.03%)  2/25 (8.00%)  2/24 (8.33%)  0/15 (0.00%) 
Gastrointestinal disorders         
Abdominal Distention † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Abdominal Pain † 1  3/33 (9.09%)  1/25 (4.00%)  3/24 (12.50%)  1/15 (6.67%) 
Anal Hemorrhage † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Anal Mucositis † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Ascites † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Bloating † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Colitis † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Colonic Hemorrhage † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Constipation † 1  8/33 (24.24%)  5/25 (20.00%)  8/24 (33.33%)  2/15 (13.33%) 
Dental Caries † 1  4/33 (12.12%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Diarrhea † 1  10/33 (30.30%)  8/25 (32.00%)  9/24 (37.50%)  2/15 (13.33%) 
Dry Mouth † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Dyspepsia † 1  4/33 (12.12%)  2/25 (8.00%)  3/24 (12.50%)  2/15 (13.33%) 
Dysphagia † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  1/15 (6.67%) 
Fecal Incontinence † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Flatulence † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Gastroesophageal Reflux Disease † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Hemorrhoids † 1  0/33 (0.00%)  2/25 (8.00%)  1/24 (4.17%)  0/15 (0.00%) 
Lip Pain † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Lower Gastrointestinal Hemorrhage † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Mucositis Oral † 1  6/33 (18.18%)  5/25 (20.00%)  3/24 (12.50%)  2/15 (13.33%) 
Nausea † 1  13/33 (39.39%)  8/25 (32.00%)  14/24 (58.33%)  2/15 (13.33%) 
Oral Pain † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Other † 1 [1]  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Other † 1 [2]  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Rectal Hemorrhage † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Small Intestinal Obstruction † 1  2/33 (6.06%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Vomiting † 1  7/33 (21.21%)  4/25 (16.00%)  3/24 (12.50%)  4/15 (26.67%) 
General disorders         
Chills † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Edema Face † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Edema Limbs † 1  10/33 (30.30%)  6/25 (24.00%)  11/24 (45.83%)  2/15 (13.33%) 
Edema Trunk † 1  0/33 (0.00%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Facial Pain † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Fatigue † 1  23/33 (69.70%)  22/25 (88.00%)  18/24 (75.00%)  5/15 (33.33%) 
Fever † 1  4/33 (12.12%)  9/25 (36.00%)  5/24 (20.83%)  1/15 (6.67%) 
Flu-Like Symptoms † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Generalized Edema † 1  5/33 (15.15%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Infusion Related Reaction † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Injection Site Reaction † 1  3/33 (9.09%)  3/25 (12.00%)  1/24 (4.17%)  1/15 (6.67%) 
Localized Edema † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Malaise † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Non-Cardiac Chest Pain † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  1/15 (6.67%) 
Other † 1 [3]  0/33 (0.00%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Pain † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Immune system disorders         
Allergic Reaction † 1  4/33 (12.12%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Autoimmune Disorder † 1 [4]  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Infections and infestations         
Bladder Infection † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Bronchial Infection † 1  1/33 (3.03%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Enterocolitis Infection † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Eye Infection † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Folliculitis † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Gum Infection † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Lung Infection † 1  2/33 (6.06%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Papulopustular Rash † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Paronychia † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Pleural Infection † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Sepsis † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Sinusitis † 1  3/33 (9.09%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Skin Infection † 1  0/33 (0.00%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Thrush † 1  3/33 (9.09%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Tooth Infection † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Upper Respiratory Infection † 1  1/33 (3.03%)  5/25 (20.00%)  4/24 (16.67%)  0/15 (0.00%) 
Urinary Tract Infection † 1  1/33 (3.03%)  3/25 (12.00%)  5/24 (20.83%)  0/15 (0.00%) 
Wound Infection † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Injury, poisoning and procedural complications         
Ankle Fracture † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Bruising † 1  1/33 (3.03%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Fall † 1  2/33 (6.06%)  2/25 (8.00%)  1/24 (4.17%)  0/15 (0.00%) 
Fracture † 1  2/33 (6.06%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Other † 1 [5]  2/33 (6.06%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Wound Complication † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Investigations         
Activated Partial Thromboplastin Time Prolonged † 1  2/33 (6.06%)  2/25 (8.00%)  5/24 (20.83%)  0/15 (0.00%) 
Alanine Aminotransferase Increased † 1  14/33 (42.42%)  14/25 (56.00%)  11/24 (45.83%)  4/15 (26.67%) 
Alkaline Phosphatase Increased † 1  13/33 (39.39%)  12/25 (48.00%)  13/24 (54.17%)  6/15 (40.00%) 
Aspartate Aminotransferase Increased † 1  1/33 (3.03%)  8/25 (32.00%)  10/24 (41.67%)  2/15 (13.33%) 
Blood Bilirubin Increased † 1  2/33 (6.06%)  6/25 (24.00%)  7/24 (29.17%)  2/15 (13.33%) 
Blood Lactate Dehydrogenase Increased † 1  2/33 (6.06%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Cardiac Troponin I Increased † 1  1/33 (3.03%)  2/25 (8.00%)  1/24 (4.17%)  0/15 (0.00%) 
Cardiac Troponin T Increased † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Creatinine Increased † 1  7/33 (21.21%)  5/25 (20.00%)  9/24 (37.50%)  1/15 (6.67%) 
Electrocardiogram QT Corrected Interval Prolonged † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
GGT Increased † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
INR Increased † 1  4/33 (12.12%)  4/25 (16.00%)  12/24 (50.00%)  0/15 (0.00%) 
Lipase Increased † 1  0/33 (0.00%)  0/25 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Lymphocyte Count Decreased † 1  24/33 (72.73%)  18/25 (72.00%)  24/24 (100.00%)  10/15 (66.67%) 
Neutrophil Count Decreased † 1  25/33 (75.76%)  19/25 (76.00%)  17/24 (70.83%)  10/15 (66.67%) 
Other † 1 [6]  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Platelet Count Decreased † 1  28/33 (84.85%)  23/25 (92.00%)  21/24 (87.50%)  11/15 (73.33%) 
Weight Loss † 1  0/33 (0.00%)  3/25 (12.00%)  0/24 (0.00%)  2/15 (13.33%) 
White Blood Cell Decreased † 1  25/33 (75.76%)  22/25 (88.00%)  20/24 (83.33%)  11/15 (73.33%) 
Metabolism and nutrition disorders         
Acidosis † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Anorexia † 1  5/33 (15.15%)  6/25 (24.00%)  6/24 (25.00%)  2/15 (13.33%) 
Dehydration † 1  1/33 (3.03%)  5/25 (20.00%)  2/24 (8.33%)  0/15 (0.00%) 
Hypercalcemia † 1  1/33 (3.03%)  2/25 (8.00%)  1/24 (4.17%)  1/15 (6.67%) 
Hyperglycemia † 1  6/33 (18.18%)  5/25 (20.00%)  7/24 (29.17%)  2/15 (13.33%) 
Hyperkalemia † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  2/15 (13.33%) 
Hyperlipidemia † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Hypermagnesemia † 1  0/33 (0.00%)  0/25 (0.00%)  2/24 (8.33%)  1/15 (6.67%) 
Hypernatremia † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  1/15 (6.67%) 
Hyperuricemia † 1  8/33 (24.24%)  5/25 (20.00%)  10/24 (41.67%)  2/15 (13.33%) 
Hypoalbuminemia † 1  15/33 (45.45%)  8/25 (32.00%)  15/24 (62.50%)  3/15 (20.00%) 
Hypocalcemia † 1  15/33 (45.45%)  7/25 (28.00%)  12/24 (50.00%)  4/15 (26.67%) 
Hypoglycemia † 1  1/33 (3.03%)  1/25 (4.00%)  4/24 (16.67%)  0/15 (0.00%) 
Hypokalemia † 1  7/33 (21.21%)  7/25 (28.00%)  10/24 (41.67%)  3/15 (20.00%) 
Hyponatremia † 1  14/33 (42.42%)  7/25 (28.00%)  12/24 (50.00%)  5/15 (33.33%) 
Hypophosphatemia † 1  6/33 (18.18%)  4/25 (16.00%)  6/24 (25.00%)  3/15 (20.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  3/33 (9.09%)  3/25 (12.00%)  2/24 (8.33%)  0/15 (0.00%) 
Back Pain † 1  4/33 (12.12%)  4/25 (16.00%)  4/24 (16.67%)  0/15 (0.00%) 
Bone Pain † 1  3/33 (9.09%)  2/25 (8.00%)  3/24 (12.50%)  2/15 (13.33%) 
Flank Pain † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Generalized Muscle Weakness † 1  4/33 (12.12%)  3/25 (12.00%)  1/24 (4.17%)  1/15 (6.67%) 
Joint Effusion † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Muscle Cramp † 1  6/33 (18.18%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Muscle Weakness Lower Limb † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Myalgia † 1  5/33 (15.15%)  7/25 (28.00%)  2/24 (8.33%)  1/15 (6.67%) 
Neck Pain † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Other † 1 [7]  2/33 (6.06%)  4/25 (16.00%)  0/24 (0.00%)  1/15 (6.67%) 
Pain in Extremity † 1  3/33 (9.09%)  2/25 (8.00%)  1/24 (4.17%)  1/15 (6.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Other † 1 [8]  3/33 (9.09%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Tumor Pain † 1  9/33 (27.27%)  3/25 (12.00%)  0/24 (0.00%)  2/15 (13.33%) 
Nervous system disorders         
Concentration Impairment † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Dizziness † 1  1/33 (3.03%)  5/25 (20.00%)  2/24 (8.33%)  0/15 (0.00%) 
Dysgeusia † 1  8/33 (24.24%)  5/25 (20.00%)  8/24 (33.33%)  0/15 (0.00%) 
Extrapyramidal Disorder † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Headache † 1  5/33 (15.15%)  5/25 (20.00%)  3/24 (12.50%)  1/15 (6.67%) 
Neuralgia † 1  1/33 (3.03%)  1/25 (4.00%)  2/24 (8.33%)  0/15 (0.00%) 
Other † 1 [9]  0/33 (0.00%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Paresthesia † 1  2/33 (6.06%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Peripheral Sensory Neuropathy † 1  9/33 (27.27%)  5/25 (20.00%)  10/24 (41.67%)  0/15 (0.00%) 
Phantom Pain † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Presyncope † 1  2/33 (6.06%)  0/25 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Spinal Cord Compression † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Syncope † 1  2/33 (6.06%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Tremor † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Psychiatric disorders         
Agitation † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Anxiety † 1  3/33 (9.09%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Confusion † 1  3/33 (9.09%)  2/25 (8.00%)  0/24 (0.00%)  1/15 (6.67%) 
Depression † 1  5/33 (15.15%)  1/25 (4.00%)  0/24 (0.00%)  1/15 (6.67%) 
Insomnia † 1  2/33 (6.06%)  3/25 (12.00%)  2/24 (8.33%)  1/15 (6.67%) 
Irritability † 1  0/33 (0.00%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Renal and urinary disorders         
Acute Kidney Injury † 1  0/33 (0.00%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Dysuria † 1  1/33 (3.03%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Hematuria † 1  9/33 (27.27%)  3/25 (12.00%)  8/24 (33.33%)  0/15 (0.00%) 
Proteinuria † 1  7/33 (21.21%)  7/25 (28.00%)  7/24 (29.17%)  0/15 (0.00%) 
Renal Calculi † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Urinary Frequency † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Urinary Incontinence † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Urinary Retention † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Reproductive system and breast disorders         
Genital Edema † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Other † 1 [10]  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Pelvic Pain † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Vaginal Hemorrhage † 1 [11]  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Allergic Rhinitis † 1  1/33 (3.03%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Cough † 1  5/33 (15.15%)  6/25 (24.00%)  5/24 (20.83%)  2/15 (13.33%) 
Dyspnea † 1  15/33 (45.45%)  5/25 (20.00%)  6/24 (25.00%)  3/15 (20.00%) 
Epistaxis † 1  6/33 (18.18%)  6/25 (24.00%)  3/24 (12.50%)  3/15 (20.00%) 
Hoarseness † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Hypoxia † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Laryngeal Hemorrhage † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Laryngeal Inflammation † 1  1/33 (3.03%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Nasal Congestion † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Other † 1 [12]  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Pleural Effusion † 1  2/33 (6.06%)  1/25 (4.00%)  3/24 (12.50%)  2/15 (13.33%) 
Pneumothorax † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  1/15 (6.67%) 
Postnasal Drip † 1  0/33 (0.00%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Productive Cough † 1  2/33 (6.06%)  2/25 (8.00%)  1/24 (4.17%)  0/15 (0.00%) 
Pulmonary Edema † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Respiratory Failure † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Rhinorrhea † 1  2/33 (6.06%)  2/25 (8.00%)  0/24 (0.00%)  0/15 (0.00%) 
Sore Throat † 1  1/33 (3.03%)  3/25 (12.00%)  1/24 (4.17%)  1/15 (6.67%) 
Wheezing † 1  1/33 (3.03%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia † 1  2/33 (6.06%)  2/25 (8.00%)  1/24 (4.17%)  1/15 (6.67%) 
Bullous Dermatitis † 1  1/33 (3.03%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Dry Skin † 1  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Hyperhidrosis † 1  0/33 (0.00%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Nail Changes † 1  0/33 (0.00%)  1/25 (4.00%)  4/24 (16.67%)  0/15 (0.00%) 
Nail Discoloration † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Nail Loss † 1  1/33 (3.03%)  0/25 (0.00%)  1/24 (4.17%)  0/15 (0.00%) 
Other † 1 [13]  2/33 (6.06%)  3/25 (12.00%)  0/24 (0.00%)  1/15 (6.67%) 
Palmar-Plantar Erythrodysethesia Syndrome † 1  0/33 (0.00%)  1/25 (4.00%)  1/24 (4.17%)  0/15 (0.00%) 
Pruritus † 1  1/33 (3.03%)  2/25 (8.00%)  1/24 (4.17%)  0/15 (0.00%) 
Rash Acneiform † 1  1/33 (3.03%)  0/25 (0.00%)  2/24 (8.33%)  0/15 (0.00%) 
Rash Maculo-papular † 1  2/33 (6.06%)  1/25 (4.00%)  1/24 (4.17%)  4/15 (26.67%) 
Skin Atrophy † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Skin ulceration † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  1/15 (6.67%) 
Urticaria † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Surgical and medical procedures         
Other † 1 [14]  2/33 (6.06%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Vascular disorders         
Hot Flashes † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Hypertension † 1  4/33 (12.12%)  3/25 (12.00%)  2/24 (8.33%)  0/15 (0.00%) 
Hypotension † 1  1/33 (3.03%)  4/25 (16.00%)  3/24 (12.50%)  0/15 (0.00%) 
Lymphedema † 1  1/33 (3.03%)  0/25 (0.00%)  0/24 (0.00%)  0/15 (0.00%) 
Other † 1 [15]  0/33 (0.00%)  1/25 (4.00%)  0/24 (0.00%)  0/15 (0.00%) 
Thromboembolic Event † 1 [16]  0/33 (0.00%)  3/25 (12.00%)  1/24 (4.17%)  0/15 (0.00%) 
1
Term from vocabulary, CTCAE (Unspecified)
†
Indicates events were collected by systematic assessment
[1]
Hematochezia, Generalized GI Bleed
[2]
Tooth Extraction
[3]
Pain at Injection Site
[4]
Celiac Disease
[5]
Twisted Knee, Ankle Sprain, Port Site Bleed
[6]
Ammonia Levels Increased
[7]
Muscle "tightness", left hand pain, R axillary pain, R neck stiffness, R flank pain, "frozen thumb", hip pain
[8]
Palpable Lump RUE, Skin Pailloma R Hallux, Tumor Progression, Vaginal Cyst
[9]
Cerebral Hemorrhage, Plantar Sensitivity
[10]
Groin Pain
[11]
Spotting
[12]
Chest Pressure with Exertion
[13]
Rash NOS, Nail Bed Pain, Feet Peeling, petechial rash
[14]
minor gum transplant
[15]
Peripheral Edema
[16]
Deep Vein Thrombosis, Pulmonary Embolism
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Brian A. Van Tine, M.D., Ph.D.
Organization: Washington University School of Medicine
Phone: 314-747-3096
EMail: bvantine@wustl.edu
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03449901    
Other Study ID Numbers: 201912062-1001
1R01CA227115-01A1 ( U.S. NIH Grant/Contract )
First Submitted: February 20, 2018
First Posted: February 28, 2018
Results First Submitted: July 3, 2023
Results First Posted: September 8, 2023
Last Update Posted: September 8, 2023