Trial Outcomes & Findings for Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma (NCT NCT01055314)

NCT ID: NCT01055314

Last Updated: 2017-08-29

Results Overview

Proportion of no Grade 3+ cardiac toxicity.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

175 participants

Primary outcome timeframe

From start to week 26 of therapy

Results posted on

2017-08-29

Participant Flow

The number of participants started is 175. Eight patients were declared ineligible by the study chair, and one patient didn't receive treatment.

Participant milestones

Participant milestones
Measure	IMC-A12 IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide Add temozolomide to vincristine/irinotecan cycles.
Overall Study STARTED	100	75
Overall Study COMPLETED	55	37
Overall Study NOT COMPLETED	45	38

Reasons for withdrawal

Reasons for withdrawal
Measure	IMC-A12 IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide Add temozolomide to vincristine/irinotecan cycles.
Overall Study Adverse Event	7	4
Overall Study Death	2	1
Overall Study Lack of Efficacy	11	19
Overall Study Physician Decision	10	5
Overall Study Withdrawal by Subject	1	0
Overall Study Ineligible	3	5
Overall Study Refusal of further protocol therapy	10	4
Overall Study No treatment	1	0

Baseline Characteristics

Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IMC-A12 n=100 Participants IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide n=75 Participants Add temozolomide to vincristine/irinotecan cycles.	Total n=175 Participants Total of all reporting groups
Age, Continuous	161.93 Months STANDARD_DEVIATION 67.36 • n=5 Participants	152.04 Months STANDARD_DEVIATION 79.20 • n=7 Participants	157.69 Months STANDARD_DEVIATION 72.62 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	30 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	45 Participants n=7 Participants	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	55 Participants n=7 Participants	132 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	74 Participants n=5 Participants	53 Participants n=7 Participants	127 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start to week 26 of therapy

Population: 18 participants were excluded because of ineligibility or insufficient information to assess feasibility.

Proportion of no Grade 3+ cardiac toxicity.

Outcome measures

Outcome measures
Measure	IMC-A12 n=82 Participants IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide Add temozolomide to vincristine/irinotecan cycles.
Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment	0.9390 Proportion of Participants Interval 0.8872 to 0.9908	—

PRIMARY outcome

Timeframe: From start to week 26 of therapy

Population: 13 participants were excluded because of ineligibility or insufficient information to assess feasibility.

Proportion of no Grade 4+ non-hematologic toxicity.

Outcome measures

Outcome measures
Measure	IMC-A12 n=62 Participants IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide Add temozolomide to vincristine/irinotecan cycles.
Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment	0.7097 Proportion of Participants Interval 0.5967 to 0.8227	—

PRIMARY outcome

Timeframe: Up to 54 weeks

Population: 9 participants who were ineligible or did not receive treatment were excluded.

Number of patients with grade 3+ adverse events (AE) during therapy. (Grade 3+) = (Grade 3 + Grade 4 + Grade 5) . Grade 3: Severe and undesirable AE; Grade 4: Life threatening or disabling AE; Grade 5: Death related to AE.

Outcome measures

Outcome measures
Measure	IMC-A12 n=96 Participants IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide n=70 Participants Add temozolomide to vincristine/irinotecan cycles.
Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0	89 Participants	61 Participants

PRIMARY outcome

Timeframe: 3 years

Population: 9 participants who were ineligible or did not receive treatment were excluded.

Probability of no relapse, secondary malignancy, or death after 3 years in the study.

Outcome measures

Outcome measures
Measure	IMC-A12 n=96 Participants IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide n=70 Participants Add temozolomide to vincristine/irinotecan cycles.
Event-Free Survival	0.1627 Probability Interval 0.0747 to 0.2507	0.1919 Probability Interval 0.0407 to 0.3431

SECONDARY outcome

Timeframe: From the start of treatment until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities

Population: 20 participants were excluded because of ineligibility or absence in overall response evaluation.

Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at \> 4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	IMC-A12 n=90 Participants IMC-A12 + Multi-agent intensive chemotherapy regimen.	Temozolomide n=65 Participants Add temozolomide to vincristine/irinotecan cycles.
Response Rate (CR + PR)	0.7667 Proportion of Participants Interval 0.6793 to 0.854	0.7846 Proportion of Participants Interval 0.6847 to 0.8846

Adverse Events

Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)

Serious events: 79 serious events

Other events: 85 other events

Deaths: 0 deaths

Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)

Serious events: 40 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab) n=96 participants at risk Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50 \& 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47 \& 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, \& 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28 \& 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41 \& 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41 \& 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24. Cixutumumab: Given IV Cyclophosphamide: Given IV Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Vincristine Sulfate	Group 2 (Chemotherapy, Radiation Therapy, Temozolomide) n=70 participants at risk Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50. Cyclophosphamide: Given IV Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO Vincristine Sulfate Liposome: Given IV
Gastrointestinal disorders Abdominal distension	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Abdominal pain	5.2% 5/96 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Renal and urinary disorders Acute kidney injury	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Alanine aminotransferase increased	9.4% 9/96 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Alkaline phosphatase increased	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Immune system disorders Allergic reaction	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Anal ulcer	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Blood and lymphatic system disorders Anemia	4.2% 4/96 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Metabolism and nutrition disorders Anorexia	4.2% 4/96 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Respiratory, thoracic and mediastinal disorders Apnea	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Appendicitis	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Ascites	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Aspartate aminotransferase increased	5.2% 5/96 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Blood bilirubin increased	3.1% 3/96 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Blood and lymphatic system disorders Bone marrow hypocellular	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Cardiac disorders Cardiac arrest	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Catheter related infection	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Colitis	5.2% 5/96 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
General disorders Death NOS	31.2% 30/96 • Number of events 30 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	42.9% 30/70 • Number of events 30 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Metabolism and nutrition disorders Dehydration	7.3% 7/96 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Psychiatric disorders Delirium	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Nervous system disorders Depressed level of consciousness	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Injury, poisoning and procedural complications Dermatitis radiation	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Diarrhea	8.3% 8/96 • Number of events 8 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Ejection fraction decreased	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Endocrine disorders Endocrine disorders - Other, specify	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Enterocolitis infectious	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Respiratory, thoracic and mediastinal disorders Epistaxis	1.0% 1/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Esophageal infection	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Esophageal pain	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Esophageal stenosis	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Esophagitis	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Blood and lymphatic system disorders Febrile neutropenia	7.3% 7/96 • Number of events 12 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
General disorders Fever	1.0% 1/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Injury, poisoning and procedural complications Fracture	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Gastric hemorrhage	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations GGT increased	3.1% 3/96 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).

Other adverse events
Measure	Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab) n=96 participants at risk Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50 \& 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47 \& 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, \& 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28 \& 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41 \& 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41 \& 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24. Cixutumumab: Given IV Cyclophosphamide: Given IV Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Vincristine Sulfate	Group 2 (Chemotherapy, Radiation Therapy, Temozolomide) n=70 participants at risk Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50. Cyclophosphamide: Given IV Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO Vincristine Sulfate Liposome: Given IV
Gastrointestinal disorders Abdominal distension	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Abdominal infection	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Abdominal pain	7.3% 7/96 • Number of events 8 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	11.4% 8/70 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Metabolism and nutrition disorders Acidosis	1.0% 1/96 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Activated partial thromboplastin time prolonged	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Renal and urinary disorders Acute kidney injury	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Psychiatric disorders Agitation	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Alanine aminotransferase increased	15.6% 15/96 • Number of events 22 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	21.4% 15/70 • Number of events 22 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Alkaline phosphatase increased	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Metabolism and nutrition disorders Alkalosis	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Immune system disorders Allergic reaction	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Anal fistula	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Anal hemorrhage	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Anal mucositis	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Anal pain	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	4.3% 3/70 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Immune system disorders Anaphylaxis	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Blood and lymphatic system disorders Anemia	9.4% 9/96 • Number of events 11 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	5.7% 4/70 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Metabolism and nutrition disorders Anorexia	15.6% 15/96 • Number of events 18 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	17.1% 12/70 • Number of events 14 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Psychiatric disorders Anxiety	5.2% 5/96 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Ascites	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Aspartate aminotransferase increased	9.4% 9/96 • Number of events 12 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	15.7% 11/70 • Number of events 14 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Musculoskeletal and connective tissue disorders Back pain	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	7.1% 5/70 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Renal and urinary disorders Bladder spasm	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Blood bilirubin increased	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Eye disorders Blurred vision	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Musculoskeletal and connective tissue disorders Bone pain	3.1% 3/96 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Bronchial infection	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Infections and infestations Catheter related infection	7.3% 7/96 • Number of events 8 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	2.9% 2/70 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Musculoskeletal and connective tissue disorders Chest wall pain	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Colitis	7.3% 7/96 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	12.9% 9/70 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Psychiatric disorders Confusion	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Congenital, familial and genetic disorders Congenital, familial and genetic disorders - Other, specify	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Gastrointestinal disorders Constipation	9.4% 9/96 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	5.7% 4/70 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations CPK increased	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Investigations Creatinine increased	2.1% 2/96 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Metabolism and nutrition disorders Dehydration	9.4% 9/96 • Number of events 9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	4.3% 3/70 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Nervous system disorders Depressed level of consciousness	0.00% 0/96 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	1.4% 1/70 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Psychiatric disorders Depression	1.0% 1/96 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	0.00% 0/70 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Injury, poisoning and procedural complications Dermatitis radiation	3.1% 3/96 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).	7.1% 5/70 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).