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High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies

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ClinicalTrials.gov Identifier: NCT03146962
Recruitment Status : Completed
First Posted : May 10, 2017
Results First Posted : May 2, 2024
Last Update Posted : May 2, 2024
Sponsor:
Collaborator:
Stand Up To Cancer
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Colorectal Cancer
Pancreatic Cancer
Lung Cancer
Intervention Drug: Vitamin C
Enrollment 61
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort A: Vitamin C + Surgery Cohort B: Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Hide Arm/Group Description

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

 Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
Period Title: Overall Study
Started 7 21 3 3 4 3 3 7 3 7
Completed 5 15 3 3 3 3 3 6 3 6
Not Completed 2 6 0 0 1 0 0 1 0 1
Reason Not Completed
Lost to Follow-up             1             1             0             0             0             0             0             0             0             0
Adverse Event             0             3             0             0             0             0             0             1             0             0
Withdrawal by Subject             0             0             0             0             1             0             0             0             0             0
Death             0             1             0             0             0             0             0             0             0             0
COVID Precautions             1             0             0             0             0             0             0             0             0             0
Physician Decision             0             0             0             0             0             0             0             0             0             1
Started New Treatment             0             1             0             0             0             0             0             0             0             0
Arm/Group Title Cohort A: Vitamin C + Surgery Cohort B: Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8 Total
Hide Arm/Group Description

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

 Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. Total of all reporting groups
Overall Number of Baseline Participants 7 21 3 3 4 3 3 7 3 7 61
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 7 participants 21 participants 3 participants 3 participants 4 participants 3 participants 3 participants 7 participants 3 participants 7 participants 61 participants
49.02
(44.09 to 77.89)
60.72
(40.98 to 87.84)
54.51
(48.49 to 71.18)
55.5
(42.51 to 71.66)
75.66
(69.04 to 77.85)
48.46
(46.86 to 65.21)
77.73
(68.09 to 79.43)
58.05
(43.96 to 70.74)
69.92
(66.11 to 69.92)
58.94
(50.15 to 74.46)
61.66
(40.98 to 87.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 21 participants 3 participants 3 participants 4 participants 3 participants 3 participants 7 participants 3 participants 7 participants 61 participants
Female
5
  71.4%
14
  66.7%
1
  33.3%
1
  33.3%
2
  50.0%
0
   0.0%
2
  66.7%
3
  42.9%
1
  33.3%
2
  28.6%
31
  50.8%
Male
2
  28.6%
7
  33.3%
2
  66.7%
2
  66.7%
2
  50.0%
3
 100.0%
1
  33.3%
4
  57.1%
2
  66.7%
5
  71.4%
30
  49.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 21 participants 3 participants 3 participants 4 participants 3 participants 3 participants 7 participants 3 participants 7 participants 61 participants
Hispanic or Latino
1
  14.3%
4
  19.0%
0
   0.0%
1
  33.3%
2
  50.0%
1
  33.3%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
10
  16.4%
Not Hispanic or Latino
6
  85.7%
16
  76.2%
3
 100.0%
2
  66.7%
2
  50.0%
2
  66.7%
3
 100.0%
7
 100.0%
2
  66.7%
7
 100.0%
50
  82.0%
Unknown or Not Reported
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 21 participants 3 participants 3 participants 4 participants 3 participants 3 participants 7 participants 3 participants 7 participants 61 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  14.3%
4
   6.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   4.8%
0
   0.0%
1
  33.3%
1
  25.0%
0
   0.0%
0
   0.0%
2
  28.6%
0
   0.0%
1
  14.3%
6
   9.8%
White
5
  71.4%
14
  66.7%
3
 100.0%
2
  66.7%
2
  50.0%
3
 100.0%
3
 100.0%
5
  71.4%
2
  66.7%
5
  71.4%
44
  72.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  14.3%
6
  28.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7
  11.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 21 participants 3 participants 3 participants 4 participants 3 participants 3 participants 7 participants 3 participants 7 participants 61 participants
7 21 3 3 4 3 3 7 3 7 61
1.Primary Outcome
Title Pathologic Response Based on Tumor Regression Grading in Cohort A Patients
Hide Description Number of patients with partial or complete pathological response in surgically resected tumor tissue: Pathological response rate is the number of patients with partial or complete pathological response in surgically resected tumor tissue. Pathologic response was assessed by tumor regression grade. This is a pathologic assessment of the amount of residual cancer cells in the specimen and the degree of fibrosis in the sample specimen. A completer response is 0% residual cancer cells. A partial response is 10-50% residual cancer cells, and no response is >50% residual cancer cells within the tumor specimen.
Time Frame cohort A - 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Only the 6 patients who had surgery from Cohort A, and thus had evaluable tissue, were analyzed for this measure. Participants in Cohort B and C did not undergo surgery, and were thus not evaluable.
Arm/Group Title Cohort A: Vitamin C + Surgery
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
2.Primary Outcome
Title 3-month Disease Control Rate (DCR) Will be Evaluated Using RECIST v 1.1 in Cohort B Patients.
Hide Description Percentage of patients with complete response, partial response, or stable disease as a result of their therapy at 3 months
Time Frame Cohort B - 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
DCR was not collected for Cohort A or Cohort C. 5 participants from Cohort B were missing scans and were therefor unevaluable.
Arm/Group Title Cohort B: Vitamin C Only
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Overall Number of Participants Analyzed 16
Measure Type: Count of Participants
Unit of Measure: Participants
1
   6.3%
3.Primary Outcome
Title Maximal Tolerated Dose of High Dose Vitamin C in Combination With Y90 Radioembolization
Hide Description Maximal tolerated dose will be evaluated by assessment of dose limiting toxicities for multiple dose levels. Dose limiting toxicity will be defined as any grade 3-4 adverse event possibly, probably, or definitely attributed to vitamin C therapy in the 21 days of protocol therapy. In any group of 3 patients, if one patient experiences dose limiting toxicity, the group will be expanded by 3 additional patients (eg. 6 for that group). If, at any dose level, 2 or more patients experience a dose limiting toxicity, the maximal tolerated dose will be reached, and further dose escalation will not be pursued. The dose level may then be expanded up to 10 additional patients to confirm the safety and toxicity at that dose level.
Time Frame Cohort C - 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients that received a dose of Vitamin C in Cohort C were considered evaluable. In Cohort C, 30 out of 32 participants who received vitamin C were evaluated across dose levels. Cohort A and B were not dose escalations, and therefore were not evaluated for maximum tolerated dose.
Arm/Group Title Cohort C: Vitamin C + Y-90 (All Dose Levels)
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at for 4 days per week for 1-4 weeks. Vitamin C will also be administered the same day as, or within 24 hours prior to, Y90 radioembolization of hepatic metastases.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: g/kg
Vitamin C Weekly Infusion Dose 1.25
Vitamin C Infusion Dose the Day of Y-90 Radioembolization 1.25
4.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS is defined as the time from registration to cancer progression or death due to any cause for up to 6 months. Cancer progression is defined using the Response Evaluation Criteria in Solid Tumors v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in non-target lesions, or the appearance of new lesions.
Time Frame cohort B - up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohort A and Cohort C were not assessed for PFS. 5 participants were missing scans from Cohort B and were therefore unevaluable.
Arm/Group Title Cohort B: Vitamin C Only
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: days
36
(14 to 151)
5.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description Number of patients with a partial response or complete response based on RECIST 1.1 Criteria.
Time Frame cohort B - up to 6 months cohort C - 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
For Cohort B, only 16/21 participants had complete sets of imaging scans and were therefore evaluable. Participants in Cohort A were not evaluated for ORR. In Cohort C Dose Level 3, one patient withdrew from the study early and therefore was unevaluable. For cohort C dose level 6, three patients did not have complete imaging to be evaluable. For Cohort C Dose Level one participant withdrew prior to treatment and one participant was missing scans, therefore they were not unevaluable.
Arm/Group Title Cohort B: Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.
Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.
Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.
Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.
A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
Overall Number of Participants Analyzed 16 3 3 3 3 3 4 3 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
1
  33.3%
0
   0.0%
6.Secondary Outcome
Title Time to Maximum Concentration and Half-life of Vitamin C (t1/2) in Hours in Cohort B
Hide Description The serum concentration of vitamin C was serially measured following vitamin C infusion at 1.25 g/kg at various timepoints up to 24 hours post infusion to determine the Tmax and t(1/2) in hours
Time Frame Up to 24 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics data was not assessed for Cohort A or Cohort C. PK samples for 5 participants from Cohort B were not obtained and therefore only 16/21 participants were evaluable.
Arm/Group Title Cohort B: Vitamin C Only
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: hours
T(max) 2.28  (0.38)
t(1/2) 6.46  (1.44)
7.Secondary Outcome
Title Safety of High Dose Vitamin C Administration Using CTCAE 4.03.
Hide Description The number of participants per cohort who experienced a Grade 3 or 4 adverse event (as defined by CTCAE v4.03) that was deemed possibly, probably, or definitely related to Vitamin C.
Time Frame Adverse events were assessed from the start of study treatment to 30 days after the last infusion of vitamin C. For Cohort A and C, this was approximately 2 months. For Cohort B this was about a 6 month duration.
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants analyzed includes any participants that were enrolled in the study and received at least one dose of Vitamin C.
Arm/Group Title Cohort A: Vitamin C + Surgery Cohort B: Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.
Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.
Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.
Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.
A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
Overall Number of Participants Analyzed 7 19 3 3 4 3 3 7 3 6
Measure Type: Count of Participants
Unit of Measure: Participants
Alkaline Phosphatase Increase
0
   0.0%
2
  10.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Aspartate Aminotransferase Increase
0
   0.0%
2
  10.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
  42.9%
0
   0.0%
0
   0.0%
Alanine Aminotransferase Increase
0
   0.0%
3
  15.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Anemia
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
  16.7%
Hypokalemia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Blood Bilirubin Increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Hypertension
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Fatigue
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Generalized Muscle Weakness
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
Confusion
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Scrotal Pain
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Syncope
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hemolysis
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Maximum Concentration of Vitamin C in Hours in Cohort B
Hide Description The serum concentration of vitamin C was serially measured following vitamin C infusion at 1.25 g/kg at various timepoints up to 24 hours post infusion to determine the maximum concentration (Cmax) in mM.
Time Frame Up to 24 hours post-infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics were not assessed for Cohort A and C. PK samples for 5 participants from Cohort B were not obtained and therefore only 16/21 participants were evaluable.
Arm/Group Title Cohort B: Vitamin C Only
Hide Arm/Group Description:

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: mM
41.19  (10.89)
9.Other Pre-specified Outcome
Title In Vitro Activity of Vitamin C in Tumor Organoids
Hide Description Molecular signature of vitamin C efficacy will be determined using RNA sequencing and compared between KRAS or BRAF mutant vs wild type tumors. Organoids will be prepared from resected tumor samples and treated with vitamin C.
Time Frame cohort A - 8 weeks, cohort B - up to 6 months
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Exploratory Biomarker Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol
Hide Description To explore potential correlation of gene expression pattern with anti-tumor activity of vitamin C, we plan to perform RNA sequencing using surgical sample in cohort A patients who will receive vitamin C infusion pre-operatively.
Time Frame cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Pharmacodynamic Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol.
Hide Description Immunohistochemical (IHC) staining for GLUT1 protein expression will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues. Immunohistochemical (IHC) staining for phosphor-AMPK will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues to assess AMPK activation.
Time Frame cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks
Outcome Measure Data Not Reported
Time Frame Adverse events were assessed from the start of study treatment to 30 days after the last infusion of vitamin C. For Cohort A and C, this was approximately 2 months. For Cohort B this was about a 6 month duration. Some study participants were enrolled in the trial, but did not receive study treatment, so they are not included in the at risk population.
Adverse Event Reporting Description All enrolled participants were assessed for death. Only participants treated were assessed for adverse events. Two participants that were enrolled in Cohort B Vitamin C Only were withdrawn prior to receiving study treatment. One participant that was enrolled in Vitamin C + Y-90: Dose Level 8 was withdrawn from the study before receiving study treatment. Therefore they were not included in the at risk population for adverse events, only mortality.
 
Arm/Group Title Cohort A: Vitamin C + Surgery Cohort B Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Hide Arm/Group Description

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

 Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.
All-Cause Mortality
Cohort A: Vitamin C + Surgery Cohort B Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   1/21 (4.76%)   0/3 (0.00%)   0/3 (0.00%)   0/4 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   2/7 (28.57%)   0/3 (0.00%)   1/7 (14.29%) 
Hide Serious Adverse Events
Cohort A: Vitamin C + Surgery Cohort B Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   4/19 (21.05%)   0/3 (0.00%)   0/3 (0.00%)   0/4 (0.00%)   0/3 (0.00%)   0/3 (0.00%)   4/7 (57.14%)   0/3 (0.00%)   2/6 (33.33%) 
Blood and lymphatic system disorders                     
Anemia * 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  1/6 (16.67%) 
Hemolysis † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cardiac disorders                     
Atrial Fibrillation † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                     
Abdominal Pain † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Vomiting † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Abdominal Distension † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
General disorders                     
Fever † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications                     
Wound Infection † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders                     
Anorexia † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Generalized Muscle Weakness † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders                     
Syncope † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Psychiatric disorders                     
Confusion † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Reproductive system and breast disorders                     
Scrotal Pain † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders                     
Dyspnea † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
1
Term from vocabulary, CTCAE v4.03
*
Indicates events were collected by non-systematic assessment
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort A: Vitamin C + Surgery Cohort B Vitamin C Only Cohort C: Vitamin C + Y-90 Dose Level 1 Cohort C: Vitamin C + Y-90 Dose Level 2 Cohort C: Vitamin C + Y-90 Dose Level 3 Cohort C: Vitamin C + Y-90 Dose Level 4 Cohort C: Vitamin C + Y-90 Dose Level 5 Cohort C: Vitamin C + Y-90 Dose Level 6 Cohort C: Vitamin C + Y-90 Dose Level 7 Cohort C: Vitamin C + Y-90 Dose Level 8
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/7 (85.71%)   18/19 (94.74%)   3/3 (100.00%)   3/3 (100.00%)   3/4 (75.00%)   3/3 (100.00%)   3/3 (100.00%)   7/7 (100.00%)   2/3 (66.67%)   5/6 (83.33%) 
Blood and lymphatic system disorders                     
Anemia † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  2/3 (66.67%)  4/7 (57.14%)  0/3 (0.00%)  4/6 (66.67%) 
Cardiac disorders                     
Other: Chest tightness/discomfort † 1  0/7 (0.00%)  0/19 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Tachycardia, unspecified † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                     
Abdominal pain * 1  2/7 (28.57%)  7/19 (36.84%)  2/3 (66.67%)  2/3 (66.67%)  1/4 (25.00%)  2/3 (66.67%)  2/3 (66.67%)  4/7 (57.14%)  0/3 (0.00%)  1/6 (16.67%) 
Constipation * 1  1/7 (14.29%)  3/19 (15.79%)  1/3 (33.33%)  2/3 (66.67%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/3 (0.00%)  2/6 (33.33%) 
Vomiting † 1  1/7 (14.29%)  4/19 (21.05%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  3/7 (42.86%)  0/3 (0.00%)  2/6 (33.33%) 
Nausea † 1  1/7 (14.29%)  5/19 (26.32%)  0/3 (0.00%)  2/3 (66.67%)  1/4 (25.00%)  2/3 (66.67%)  0/3 (0.00%)  2/7 (28.57%)  0/3 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders Other, Bleeding Gums † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Anal Hemorrhage † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Other: Blood in Stool † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Abdominal distension † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Bleeding Gums † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Bloating † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Diarrhea † 1  0/7 (0.00%)  2/19 (10.53%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  1/3 (33.33%)  0/6 (0.00%) 
Other: Dry Heaves † 1  0/7 (0.00%)  2/19 (10.53%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Flatulence † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ascites † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
General disorders                     
Fatigue † 1  2/7 (28.57%)  6/19 (31.58%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  2/3 (66.67%)  2/3 (66.67%)  4/7 (57.14%)  1/3 (33.33%)  2/6 (33.33%) 
Fever † 1  0/7 (0.00%)  2/19 (10.53%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Pain † 1  0/7 (0.00%)  3/19 (15.79%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  0/3 (0.00%)  0/6 (0.00%) 
Edema Limbs † 1  1/7 (14.29%)  1/19 (5.26%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  2/6 (33.33%) 
Other: Cold Intolerance † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Flu Like Symptoms † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Activity Change † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Chest Pain, unspecified † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Chills † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Diaphoresis † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Edema face † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Other: "Feeling Shaky" † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Night Sweats † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Increased Thirst † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Appetite Change † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Jaundice † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders                     
Portal Vein Thrombosis † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications                     
Fall † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Investigations                     
Alkaline phosphatase increased † 1  2/7 (28.57%)  5/19 (26.32%)  2/3 (66.67%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  2/3 (66.67%)  5/7 (71.43%)  1/3 (33.33%)  1/6 (16.67%) 
Alanine aminotransferase increased † 1  1/7 (14.29%)  4/19 (21.05%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  7/7 (100.00%)  1/3 (33.33%)  0/6 (0.00%) 
Blood bilirubin increased † 1  1/7 (14.29%)  2/19 (10.53%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  3/7 (42.86%)  0/3 (0.00%)  0/6 (0.00%) 
Hypokalemia † 1  0/7 (0.00%)  4/19 (21.05%)  0/3 (0.00%)  0/3 (0.00%)  2/4 (50.00%)  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  3/6 (50.00%) 
Aspartate aminotransferase increased † 1  0/7 (0.00%)  4/19 (21.05%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  7/7 (100.00%)  1/3 (33.33%)  1/6 (16.67%) 
Neutrophil Count Decreased † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Increased Lactate Dehydrogenase † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Creatinine Increased † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Weight Loss † 1  0/7 (0.00%)  1/19 (5.26%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Platelet Count Decreased † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Lymphocyte Count Decreased † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Weight gain † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Ketosis † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders                     
Hypoalbuminemia † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/3 (33.33%)  2/6 (33.33%) 
Anorexia † 1  0/7 (0.00%)  2/19 (10.53%)  0/3 (0.00%)  2/3 (66.67%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Dehydration † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypomagnesemia † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Hypocalcemia † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hyperglycemia † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Flank Pain † 1  0/7 (0.00%)  2/19 (10.53%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Generalized Muscle Weakness † 1  1/7 (14.29%)  8/19 (42.11%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  1/3 (33.33%)  1/6 (16.67%) 
Neck Pain † 1  0/7 (0.00%)  0/19 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Myalgia † 1  0/7 (0.00%)  2/19 (10.53%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Back Pain † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  1/3 (33.33%)  3/4 (75.00%)  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Other: Loss of Hand Movement † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders                     
Headache † 1  0/7 (0.00%)  2/19 (10.53%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Seizure † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Peripheral Sensory Neuropathy † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Neuropathy, Type Unspecified † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  1/6 (16.67%) 
Dizziness † 1  0/7 (0.00%)  2/19 (10.53%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Syncope † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Somnolence † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Psychiatric disorders                     
Anxiety † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Insomnia † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  3/7 (42.86%)  0/3 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders                     
Urinary Frequency † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Reproductive system and breast disorders                     
Pelvic Pain † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Other: COVID-19 Infection † 1  1/7 (14.29%)  0/19 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Dyspnea † 1  0/7 (0.00%)  3/19 (15.79%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/3 (0.00%)  0/6 (0.00%) 
Upper Respiratory Infection † 1  1/7 (14.29%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cough † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Rhinorrhea † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders                     
Other: Folliculitis † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Periorbital edema † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Other: Rash (Unspecified) † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Pruritus † 1  0/7 (0.00%)  0/19 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vascular disorders                     
Hypertension † 1  0/7 (0.00%)  3/19 (15.79%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%)  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypotension † 1  0/7 (0.00%)  1/19 (5.26%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
1
Term from vocabulary, CTCAE v4.03
†
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[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: Dr. Manish Shah, Sponsor-Investigator
Organization: Weill Cornell Medicine
Phone: 646-962-6200
EMail: mas9313@med.cornell.edu
Layout table for additonal information
Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT03146962    
Other Study ID Numbers: 1610017688
First Submitted: April 27, 2017
First Posted: May 10, 2017
Results First Submitted: February 27, 2024
Results First Posted: May 2, 2024
Last Update Posted: May 2, 2024