Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT02180867

Recruitment Status : Active, not recruiting

First Posted : July 3, 2014

Results First Posted : October 9, 2020

Last Update Posted : February 15, 2024

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Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Alveolar Soft Part Sarcoma Angiomatoid Fibrous Histiocytoma Atypical Fibroxanthoma Clear Cell Sarcoma of Soft Tissue Epithelioid Malignant Peripheral Nerve Sheath Tumor Epithelioid Sarcoma Extraskeletal Myxoid Chondrosarcoma Extraskeletal Osteosarcoma Fibrohistiocytic Neoplasm Fibrosarcoma Inflammatory Myofibroblastic Tumor Intimal Sarcoma Leiomyosarcoma Liposarcoma Liver Embryonal Sarcoma Low Grade Fibromyxoid Sarcoma Low Grade Myofibroblastic Sarcoma Malignant Cutaneous Granular Cell Tumor Malignant Peripheral Nerve Sheath Tumor Malignant Triton Tumor Mesenchymal Chondrosarcoma Myxofibrosarcoma Myxoid Chondrosarcoma Myxoinflammatory Fibroblastic Sarcoma Nerve Sheath Neoplasm PEComa Pericytic Neoplasm Plexiform Fibrohistiocytic Tumor Sclerosing Epithelioid Fibrosarcoma Skin Glomus Tumor Stage IB Soft Tissue Sarcoma AJCC v7 Stage IIB Soft Tissue Sarcoma AJCC v7 Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Synovial Sarcoma Undifferentiated High Grade Pleomorphic Sarcoma of Bone
Interventions	Drug: Doxorubicin Drug: Doxorubicin Hydrochloride Drug: Ifosfamide Drug: Pazopanib Drug: Pazopanib Hydrochloride Radiation: Radiation Therapy Procedure: Therapeutic Conventional Surgery
Enrollment	140

Participant Flow

Recruitment Details
Pre-assignment Details	All patients began at Dose-Finding Level 1. Dose-Finding Level 0 CR, Dose-Finding Level 2 CR, and Dose-Finding Level 0 RT never enrolled because protocol-defined dose de-escalation and escalation parameters were not met. Cohorts C and D were closed to further patient accrual on October 12, 2017 due to slower than anticipated enrollment.


Arm/Group Title	Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Dose-Finding Level 1 CR: ...	Dose-Finding Level 1 RT: ...	Dose-Finding Level 2 RT: ...	Regimen A: Chemoradiation plus pazo...	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus p...	Regimen D: Radiation therapy alone
Arm/Group Description	Dose-Finding Level 1 CR: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 1 RT: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 2 RT: Adult: Pazopanib 800 mg; Pediatric: Pazopanib 450 mg/m2	Regimen A: Chemoradiation plus pazopanib	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus pazopanib	Regimen D: Radiation therapy alone
Period Title: Overall Study
Started	10	11	10	49	48	6	6
Pediatric Patients	6	4	3	18	19	1	0
Adult Patients	4	7	7	31	29	5	6
Completed	4	0	6	23	21	3	1
Not Completed	6	11	4	26	27	3	5
Reason Not Completed
Adverse Event	3	4	1	5	0	0	0
Death	0	0	0	0	1	0	0
Lack of Efficacy	0	2	0	1	6	0	1
Physician Decision	1	3	1	10	9	3	4
Withdrawal by Subject	0	0	0	1	1	0	0
Ineligible	1	2	0	3	5	0	0
Repeat Eligibility Studies	0	0	0	0	1	0	0
Refusal of further protocol therapy	1	0	2	6	4	0	0

Baseline Characteristics

Arm/Group Title		Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D	Total
Arm/Group Description		Dose-Finding Level 1 CR: ...	Dose-Finding Level 1 RT: ...	Dose-Finding Level 2 RT: ...	Regimen A: Chemoradiation plus pazo...	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus p...	Regimen D: Radiation therapy alone	Total of all reporting groups
Arm/Group Description		Dose-Finding Level 1 CR: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 1 RT: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 2 RT: Adult: Pazopanib 800 mg; Pediatric: Pazopanib 450 mg/m2	Regimen A: Chemoradiation plus pazopanib	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus pazopanib	Regimen D: Radiation therapy alone	Total of all reporting groups
Overall Number of Baseline Participants		10	11	10	49	48	6	6	140
Baseline Analysis Population Description		...
Baseline Analysis Population Description		It was pre-specified to combine adult and pediatric participants for analysis as they received an equivalent dose of Pazopanib. There were no patients enrolled onto Dose-Finding Level 0 CR and Dose-Finding Level 2 CR or Dose-Finding Level 0 RT.
Age, Continuous Mean (Standard Deviation) Unit of measure: Months
	Number Analyzed	10 participants	11 participants	10 participants	49 participants	48 participants	6 participants	6 participants	140 participants
		225.1 (57.8)	524.3 (270.3)	407.3 (224.7)	376.3 (243.4)	356.2 (221.8)	547.2 (260.6)	722.8 (141.9)	394.6 (242.3)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	10 participants	11 participants	10 participants	49 participants	48 participants	6 participants	6 participants	140 participants
	Female	4 40.0%	3 27.3%	3 30.0%	30 61.2%	18 37.5%	2 33.3%	3 50.0%	63 45.0%
	Male	6 60.0%	8 72.7%	7 70.0%	19 38.8%	30 62.5%	4 66.7%	3 50.0%	77 55.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	10 participants	11 participants	10 participants	49 participants	48 participants	6 participants	6 participants	140 participants
	Hispanic or Latino	2 20.0%	1 9.1%	1 10.0%	13 26.5%	9 18.8%	0 0.0%	0 0.0%	26 18.6%
	Not Hispanic or Latino	6 60.0%	9 81.8%	9 90.0%	34 69.4%	38 79.2%	6 100.0%	6 100.0%	108 77.1%
	Unknown or Not Reported	2 20.0%	1 9.1%	0 0.0%	2 4.1%	1 2.1%	0 0.0%	0 0.0%	6 4.3%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	10 participants	11 participants	10 participants	49 participants	48 participants	6 participants	6 participants	140 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%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.1%	0 0.0%	0 0.0%	1 0.7%
	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%
	Black or African American	2 20.0%	2 18.2%	1 10.0%	3 6.1%	6 12.5%	1 16.7%	0 0.0%	15 10.7%
	White	7 70.0%	8 72.7%	8 80.0%	39 79.6%	38 79.2%	5 83.3%	5 83.3%	110 78.6%
	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%
	Unknown or Not Reported	1 10.0%	1 9.1%	1 10.0%	7 14.3%	3 6.3%	0 0.0%	1 16.7%	14 10.0%

Outcome Measures

1.Primary Outcome


Title	Feasible Dose: Pediatric
Description	The dose of pazopanib that is feasible when given in combination with ...
Description	The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and < 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.
Time Frame	After the first 6 weeks of Induction

Outcome Measure Data

Analysis Population Description

Pediatric patients, excluding 1 ineligible patient in Dose-Finding CR group and 1 ineligible patient in Dose-Finding RT group


Arm/Group Title	All Pediatric Dose Finding CR Cohorts	All Pediatric Dose Finding RT Cohorts
Arm/Group Description:	Dose-Finding CR: Chemoradiation plu...	Dose-Finding RT: Radiation therapy ...
Arm/Group Description:	Dose-Finding CR: Chemoradiation plus pazopanib	Dose-Finding RT: Radiation therapy plus pazopanib
Overall Number of Participants Analyzed	5	6
Measure Type: Number Unit of Measure: milligram per square meter
	350	450

2.Primary Outcome


Title	Feasible Dose: Adult
Description	The dose of pazopanib that is feasible when given in combination with ...
Description	The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in adult unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and < 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.
Time Frame	After the first 6 weeks of Induction

Outcome Measure Data

Analysis Population Description

Adult patients, excluding 1 ineligible patient in Dose-Finding RT group


Arm/Group Title	All Adult Dose Finding CR Cohorts	All Adult Dose Finding RT Cohorts
Arm/Group Description:	Dose-Finding CR: Chemoradiation plu...	Dose-Finding RT: Radiation therapy ...
Arm/Group Description:	Dose-Finding CR: Chemoradiation plus pazopanib	Dose-Finding RT: Radiation therapy plus pazopanib
Overall Number of Participants Analyzed	4	13
Measure Type: Number Unit of Measure: milligram
	600	800

3.Primary Outcome


Title	Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13
Description	A responder is defined by more than (90% tumor necrosis at week 13). A...
Description	A responder is defined by more than (90% tumor necrosis at week 13). A non-responder has less than 90% necrosis or progressive disease before week 13.
Time Frame	Week 13 after induction

Outcome Measure Data

Analysis Population Description

It was pre-specified to combine adult and pediatric participants for analysis as they received an equivalent dose of Pazopanib. There were no patients enrolled onto Dose-Finding Level 0 CR or Dose-Finding Level 2 CR. 19 Regimen A patients and 23 Regimen B patients were excluded.


Arm/Group Title	Dose-Finding Level 1 CR	Regimen A	Regimen B
Arm/Group Description:	Dose-Finding Level 1 CR: ...	Regimen A: Chemoradiation plus pazo...	Regimen B: Chemoradiation alone
Arm/Group Description:	Dose-Finding Level 1 CR: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Regimen A: Chemoradiation plus pazopanib	Regimen B: Chemoradiation alone
Overall Number of Participants Analyzed	6	30	25
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of patients
	66.67 (28.95 to 100)	46.67 (28.81 to 64.52)	24 (7.26 to 40.74)

4.Primary Outcome


Title	Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10
Description	A responder is defined by more than 90% tumor necrosis at week 10. A n...
Description	A responder is defined by more than 90% tumor necrosis at week 10. A non-responder has less than 90% necrosis or progressive disease before week 10.
Time Frame	Week 10 after induction

Outcome Measure Data

Analysis Population Description

It was pre-specified to combine adult and pediatric participants for analysis as they received an equivalent dose of Pazopanib. There were no patients enrolled onto Dose Level 0 RT. 3 Regimen C patients excluded: 1 patient did not receive treatment and 2 missing review; 4 Regimen D patients excluded due to missing review.


Arm/Group Title	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen C	Regimen D
Arm/Group Description:	Dose-Finding Level 1 RT: ...	Dose-Finding Level 2 RT: ...	Regimen C: Radiation therapy plus p...	Regimen D: Radiation therapy alone
Arm/Group Description:	Dose-Finding Level 1 RT: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 2 RT: Adult: Pazopanib 800 mg; Pediatric: Pazopanib 450 mg/m2	Regimen C: Radiation therapy plus pazopanib	Regimen D: Radiation therapy alone
Overall Number of Participants Analyzed	3	5	3	2
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of patients
	0 (0 to 0)	40 (0 to 82.94)	0 (0 to 0)	0 (0 to 0)

5.Primary Outcome


Title	Percentage of Radiotherapy Patients Failure Free at 5 Years Following Study Entry
Description	Time to the first occurrence of relapse, progression, secondary cancer...
Description	Time to the first occurrence of relapse, progression, secondary cancer or death from any cause.
Time Frame	From enrollment to up to 60 months

Outcome Measure Data

Analysis Population Description

Data for the phase III portion of the study were never collected because the RT arm was closed earlier due to slow accrual.


Arm/Group Title	Regimen C	Regimen D
Arm/Group Description:	Regimen C: Radiation therapy plus p...	Regimen D: Radiation therapy alone
Arm/Group Description:	Regimen C: Radiation therapy plus pazopanib	Regimen D: Radiation therapy alone
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6.Secondary Outcome


Title	Percentage of Patients Local Failure Free at 5 Years Following Study Entry
Description	Defined as disease recurrence only at the primary site of disease at d...
Description	Defined as disease recurrence only at the primary site of disease at diagnosis. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
Time Frame	From enrollment to up to 60 months

Outcome Measure Data Not Reported

7.Secondary Outcome


Title	Percentage of Patients Regional Failure Free at 5 Years Following Study Entry
Description	Defined as disease recurrence at lymph nodes regional to the primary d...
Description	Defined as disease recurrence at lymph nodes regional to the primary disease site, with or without local failure but without distant failure. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
Time Frame	From enrollment to up to 60 months

Outcome Measure Data Not Reported

8.Secondary Outcome


Title	Percentage of Patients Distant Failure Free at 5 Years Following Study Entry
Description	Defined as disease recurrence at sites other than the primary site and...
Description	Defined as disease recurrence at sites other than the primary site and diagnosis and nodes regional to that site (metastatic disease, whether or not present at diagnosis), with or without loco-regional failure. The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
Time Frame	From enrollment to up to 60 months

Outcome Measure Data Not Reported

9.Secondary Outcome


Title	Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Description	Participants who experienced Grade 3 or higher toxicity was assessed b...
Description	Participants who experienced Grade 3 or higher toxicity was assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame	Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year

Outcome Measure Data

Analysis Population Description

Ineligible patients are excluded.


Arm/Group Title		Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description:		Dose-Finding Level 1 CR: ...	Dose-Finding Level 1 RT: ...	Dose-Finding Level 2 RT: ...	Regimen A: Chemoradiation plus pazo...	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus p...	Regimen D: Radiation therapy alone
Arm/Group Description:		Dose-Finding Level 1 CR: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 1 RT: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 2 RT: Adult: Pazopanib 800 mg; Pediatric: Pazopanib 450 mg/m2	Regimen A: Chemoradiation plus pazopanib	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus pazopanib	Regimen D: Radiation therapy alone
Overall Number of Participants Analyzed		9	9	10	46	43	6	6
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of patients
Pediatric Patients	Number Analyzed	5 participants	3 participants	3 participants	16 participants	18 participants	1 participants	0 participants
Pediatric Patients		60 (17.06 to 100)	66.67 (13.32 to 100)	33.33 (0 to 86.68)	75 (53.78 to 96.22)	33.33 (11.56 to 55.11)	0 (0 to 0)
Adult Patients	Number Analyzed	4 participants	6 participants	7 participants	30 participants	25 participants	5 participants	6 participants
Adult Patients		75 (32.56 to 100)	66.67 (28.95 to 100)	57.14 (20.48 to 93.80)	86.67 (74.50 to 98.83)	36 (17.18 to 54.82)	40 (0 to 82.94)	0 (0 to 0)

10.Other Pre-specified Outcome


Title	Relative Frequency of Actionable Mutations
Description	Descriptive statistical analyses will be provided to estimate the rela...
Description	Descriptive statistical analyses will be provided to estimate the relative frequency of actionable mutations across the whole cohort and within more common histological subtypes, like synovial sarcoma and malignant peripheral nerve sheath tumors.
Time Frame	At diagnosis

Outcome Measure Data Not Reported

11.Other Pre-specified Outcome


Title	Prevalence of Circulating Tumor DNA (ctDNA)
Description	Descriptive analyses will be performed to summarize the prevalence of ...
Description	Descriptive analyses will be performed to summarize the prevalence of ctDNA.
Time Frame	At diagnosis

Outcome Measure Data Not Reported

12.Other Pre-specified Outcome


Title	Mean Pharmacokinetic Parameters of Doxorubicin and Pazopanib
Description	Pharmacokinetic parameters such as the clearance of doxorubicin and pa...
Description	Pharmacokinetic parameters such as the clearance of doxorubicin and pazopanib will be estimated.
Time Frame	Up to 48 hours after the end of infusion

Outcome Measure Data Not Reported

13.Other Pre-specified Outcome


Title	Change in Fludeoxyglucose F 18 (FDG) Positron Emission Tomography (PET) Maximum Standard Uptake Value (SUVmax)
Description	To evaluate change in FDG PET maximum standard uptake value (SUVmax) f...
Description	To evaluate change in FDG PET maximum standard uptake value (SUVmax) from baseline to Week 10 or 13 in patients with unresected tumors and to correlate this change with pathologic response and EFS.
Time Frame	From enrollment to week 10 or 13 prior to tumor resection

Outcome Measure Data Not Reported

14.Other Pre-specified Outcome


Title	Relative Risk of Failure Based on Both Standard Imaging and Pathologic Assessment
Description	To compare the rate of response by standard imaging and pathologic ass...
Description	To compare the rate of response by standard imaging and pathologic assessment to determine which correlates better with local tumor control, distant tumor control, event free survival, and overall survival.
Time Frame	From enrollment up to 60 months

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Arm/Group Title	Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Dose-Finding Level 1 CR: ...	Dose-Finding Level 1 RT: ...	Dose-Finding Level 2 RT: ...	Regimen A: Chemoradiation plus pazo...	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus p...	Regimen D: Radiation therapy alone
Arm/Group Description	Dose-Finding Level 1 CR: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 1 RT: Adult: Pazopanib 600 mg; Pediatric: Pazopanib 350 mg/m2	Dose-Finding Level 2 RT: Adult: Pazopanib 800 mg; Pediatric: Pazopanib 450 mg/m2	Regimen A: Chemoradiation plus pazopanib	Regimen B: Chemoradiation alone	Regimen C: Radiation therapy plus pazopanib	Regimen D: Radiation therapy alone
All-Cause Mortality
	Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/9 (11.11%)	4/9 (44.44%)	3/10 (30.00%)	5/46 (10.87%)	9/43 (20.93%)	0/6 (0.00%)	2/6 (33.33%)
Serious Adverse Events Serious Adverse Events
	Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/9 (66.67%)	6/9 (66.67%)	2/10 (20.00%)	33/46 (71.74%)	8/43 (18.60%)	1/6 (16.67%)	0/6 (0.00%)
Blood and lymphatic system disorders
Febrile neutropenia ^† 1 [1]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	7/16 (43.75%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Anemia ^† 1 [2]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	2/30 (6.67%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Blood and lymphatic system disorders - Other, specify ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Febrile neutropenia ^† 1 [2]	1/4 (25.00%)	0/6 (0.00%)	0/7 (0.00%)	11/30 (36.67%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Cardiac disorders
Atrial fibrillation ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Atrial flutter ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Sinus tachycardia ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Eye disorders
Blurred vision ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Photophobia ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Gastrointestinal disorders
Diarrhea ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/16 (0.00%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Ileus ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Mucositis oral ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/16 (18.75%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Vomiting ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/16 (12.50%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Diarrhea ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Esophagitis ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Mucositis oral ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Nausea ^† 1 [2]	1/4 (25.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	1/5 (20.00%)	0/6 (0.00%)
Vomiting ^† 1 [2]	1/4 (25.00%)	0/6 (0.00%)	1/7 (14.29%)	2/30 (6.67%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
General disorders
Fever ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Pain ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Chills ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	1/5 (20.00%)	0/6 (0.00%)
Death NOS ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Fatigue ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	2/30 (6.67%)	0/25 (0.00%)	1/5 (20.00%)	0/6 (0.00%)
Fever ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	2/30 (6.67%)	2/25 (8.00%)	1/5 (20.00%)	0/6 (0.00%)
Gait disturbance ^† 1 [2]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
General disorders and administration site conditions - Other, specify ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Multi-organ failure ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Non-cardiac chest pain ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Hepatobiliary disorders
Perforation bile duct ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Infections and infestations
Sepsis ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/16 (0.00%)	1/18 (5.56%)	0/1 (0.00%)	0/0
Skin infection ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Wound infection ^† 1 [1]	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Sepsis ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	4/30 (13.33%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Skin infection ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	2/30 (6.67%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Upper respiratory infection ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Urinary tract infection ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Wound infection ^† 1 [2]	1/4 (25.00%)	3/6 (50.00%)	1/7 (14.29%)	1/30 (3.33%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Lung infection ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Soft tissue infection ^† 1 [2]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Device related infection ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Injury, poisoning and procedural complications
Wound dehiscence ^† 1 [1]	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/16 (6.25%)	1/18 (5.56%)	0/1 (0.00%)	0/0
Wound complication ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Wound dehiscence ^† 1 [2]	2/4 (50.00%)	0/6 (0.00%)	0/7 (0.00%)	4/30 (13.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Wound complication ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	2/30 (6.67%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Postoperative hemorrhage ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Dermatitis radiation ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Investigations
Creatinine increased ^† 1 [1]	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/16 (0.00%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Alanine aminotransferase increased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Blood bilirubin increased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Electrocardiogram QT corrected interval prolonged ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Lymphocyte count decreased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	2/30 (6.67%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Neutrophil count decreased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	5/30 (16.67%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Platelet count decreased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	5/30 (16.67%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
White blood cell decreased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	8/30 (26.67%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Ejection fraction decreased ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Metabolism and nutrition disorders
Anorexia ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/16 (12.50%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Dehydration ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/16 (12.50%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Hyperkalemia ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/16 (0.00%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Dehydration ^† 1 [2]	1/4 (25.00%)	0/6 (0.00%)	1/7 (14.29%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Hyperglycemia ^† 1 [2]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Hypokalemia ^† 1 [2]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	2/30 (6.67%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Hyponatremia ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	3/30 (10.00%)	1/25 (4.00%)	1/5 (20.00%)	0/6 (0.00%)
Hypophosphatemia ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	3/30 (10.00%)	0/25 (0.00%)	1/5 (20.00%)	0/6 (0.00%)
Musculoskeletal and connective tissue disorders
Pain in extremity ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Pain in extremity ^† 1 [2]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Nervous system disorders
Cognitive disturbance ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Dizziness ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Encephalopathy ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Headache ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Stroke ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Syncope ^† 1 [2]	1/4 (25.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Psychiatric disorders
Hallucinations ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Delirium ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	3/30 (10.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Depression ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Renal and urinary disorders
Acute kidney injury ^† 1 [1]	0/5 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/16 (0.00%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Renal and urinary disorders - Other, specify ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Reproductive system and breast disorders
Uterine hemorrhage ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Respiratory, thoracic and mediastinal disorders
Hypoxia ^† 1 [1]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Dyspnea ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Hypoxia ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Laryngospasm ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Pleural effusion ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Pneumothorax ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Pulmonary edema ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	2/30 (6.67%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Skin and subcutaneous tissue disorders
Skin hypopigmentation ^† 1 [2]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Vascular disorders
Thromboembolic event ^† 1 [1]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Thromboembolic event ^† 1 [2]	1/4 (25.00%)	1/6 (16.67%)	0/7 (0.00%)	4/30 (13.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
1 Term from vocabulary, CTCv5 † Indicates events were collected by systematic assessment [1] Pediatric [2] Adult
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Dose-Finding Level 1 CR	Dose-Finding Level 1 RT	Dose-Finding Level 2 RT	Regimen A	Regimen B	Regimen C	Regimen D
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/9 (44.44%)	2/9 (22.22%)	5/10 (50.00%)	20/46 (43.48%)	10/43 (23.26%)	1/6 (16.67%)	0/6 (0.00%)
Blood and lymphatic system disorders
Anemia ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Febrile neutropenia ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	2/25 (8.00%)	0/5 (0.00%)	0/6 (0.00%)
Cardiac disorders
Cardiac disorders - Other, specify ^† 1 [2]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
General disorders
Localized edema ^† 1 [2]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Fatigue ^† 1 [1]	0/4 (0.00%)	1/6 (16.67%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Infections and infestations
Infections and infestations - Other, specify ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Urinary tract infection ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Wound infection ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic) ^† 1 [2]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Wound dehiscence ^† 1 [2]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Wound complication ^† 1 [2]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/16 (0.00%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Wound dehiscence ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	2/7 (28.57%)	0/30 (0.00%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Wound complication ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	0/25 (0.00%)	1/5 (20.00%)	0/6 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1 [2]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	1/16 (6.25%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Lymphocyte count decreased ^† 1 [2]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	3/16 (18.75%)	2/18 (11.11%)	0/1 (0.00%)	0/0
Neutrophil count decreased ^† 1 [2]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	4/16 (25.00%)	5/18 (27.78%)	0/1 (0.00%)	0/0
Platelet count decreased ^† 1 [2]	0/5 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/16 (18.75%)	2/18 (11.11%)	0/1 (0.00%)	0/0
White blood cell decreased ^† 1 [2]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	4/16 (25.00%)	3/18 (16.67%)	0/1 (0.00%)	0/0
Alanine aminotransferase increased ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	1/7 (14.29%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Aspartate aminotransferase increased ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Lipase increased ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Lymphocyte count decreased ^† 1 [1]	1/4 (25.00%)	0/6 (0.00%)	1/7 (14.29%)	2/30 (6.67%)	3/25 (12.00%)	0/5 (0.00%)	0/6 (0.00%)
Neutrophil count decreased ^† 1 [1]	1/4 (25.00%)	0/6 (0.00%)	0/7 (0.00%)	10/30 (33.33%)	2/25 (8.00%)	0/5 (0.00%)	0/6 (0.00%)
Platelet count decreased ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	5/30 (16.67%)	2/25 (8.00%)	0/5 (0.00%)	0/6 (0.00%)
White blood cell decreased ^† 1 [1]	1/4 (25.00%)	0/6 (0.00%)	0/7 (0.00%)	6/30 (20.00%)	2/25 (8.00%)	0/5 (0.00%)	0/6 (0.00%)
Metabolism and nutrition disorders
Hyperkalemia ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Hyperphosphatemia ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	0/30 (0.00%)	1/25 (4.00%)	0/5 (0.00%)	0/6 (0.00%)
Hypokalemia ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
Vascular disorders
Hypertension ^† 1 [2]	1/5 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/16 (0.00%)	0/18 (0.00%)	0/1 (0.00%)	0/0
Hypertension ^† 1 [1]	0/4 (0.00%)	1/6 (16.67%)	1/7 (14.29%)	0/30 (0.00%)	0/25 (0.00%)	1/5 (20.00%)	0/6 (0.00%)
Hypotension ^† 1 [1]	0/4 (0.00%)	0/6 (0.00%)	0/7 (0.00%)	1/30 (3.33%)	0/25 (0.00%)	0/5 (0.00%)	0/6 (0.00%)
1 Term from vocabulary, CTCv5 † Indicates events were collected by systematic assessment [1] Adult [2] Pediatric

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Results Reporting Coordinator
Organization:	Children's Oncology Group
Phone:	626-447-0064
EMail:	resultsreportingcoordinator@childrensoncologygroup.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Avutu V, Weiss AR, Reed DR, Ahmed SK, Allen-Rhoades WA, Chen YE, Davis LE, Eaton BR, Hawkins DS, Indelicato DJ, Patel SR, Randall RL, Reinke DK, Riedel RF, Scharschmidt TJ, Thornton KA, Wang D, Janeway KA, Kopp LM. Identified Enrollment Challenges of Adolescent and Young Adult Patients on the Nonchemotherapy Arm of Children's Oncology Group Study ARST1321. J Adolesc Young Adult Oncol. 2022 Jun;11(3):328-332. doi: 10.1089/jayao.2021.0103. Epub 2021 Sep 9.

Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

Weiss AR, Chen YL, Scharschmidt TJ, Chi YY, Tian J, Black JO, Davis JL, Fanburg-Smith JC, Zambrano E, Anderson J, Arens R, Binitie O, Choy E, Davis JW, Hayes-Jordan A, Kao SC, Kayton ML, Kessel S, Lim R, Meyer WH, Million L, Okuno SH, Ostrenga A, Parisi MT, Pryma DA, Randall RL, Rosen MA, Schlapkohl M, Shulkin BL, Smith EA, Sorger JI, Terezakis S, Hawkins DS, Spunt SL, Wang D. Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2020 Aug;21(8):1110-1122. doi: 10.1016/S1470-2045(20)30325-9. Epub 2020 Jul 20.

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT02180867
Other Study ID Numbers:	NCI-2014-01340 NCI-2014-01340 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ARST1321 s14-02023 ARST1321 ( Other Identifier: Children's Oncology Group ) ARST1321 ( Other Identifier: CTEP ) U10CA180830 ( U.S. NIH Grant/Contract ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted:	July 1, 2014
First Posted:	July 3, 2014
Results First Submitted:	June 24, 2020
Results First Posted:	October 9, 2020
Last Update Posted:	February 15, 2024

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