Trial Outcomes & Findings for Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma (NCT NCT00354835)

NCT ID: NCT00354835

Last Updated: 2023-01-31

Results Overview

Probability of no relapse, secondary malignancy, or death after 4 year in the study

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

481 participants

Primary outcome timeframe

4 years

Results posted on

2023-01-31

Participant Flow

481 excludes 33 ineligible cases (declared by the Study Chair) .

Participant milestones

Participant milestones
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
Overall Study STARTED	239	242
Overall Study COMPLETED	187	181
Overall Study NOT COMPLETED	52	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
Overall Study Death	1	1
Overall Study Physician Decision	8	13
Overall Study Withdrawal by Subject	2	1
Overall Study Ineligible	17	16
Overall Study Disease progression or relapse	15	22
Overall Study Adverse Event	6	0
Overall Study Refusal of further therapy	3	8

Baseline Characteristics

Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=239 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	VAC Alternating With Vincristine, Irinotecan (VI) n=242 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	Total n=481 Participants Total of all reporting groups
Age, Continuous	89.85 months STANDARD_DEVIATION 73.39 • n=5 Participants	97.86 months STANDARD_DEVIATION 82.66 • n=7 Participants	93.88 months STANDARD_DEVIATION 78.21 • n=5 Participants
Sex: Female, Male Female	109 Participants n=5 Participants	113 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	130 Participants n=5 Participants	129 Participants n=7 Participants	259 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	39 Participants n=5 Participants	28 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	191 Participants n=5 Participants	204 Participants n=7 Participants	395 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	37 Participants n=5 Participants	29 Participants n=7 Participants	66 Participants n=5 Participants
Race (NIH/OMB) White	165 Participants n=5 Participants	181 Participants n=7 Participants	346 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	28 Participants n=5 Participants	23 Participants n=7 Participants	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 years

Probability of no relapse, secondary malignancy, or death after 4 year in the study

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=226 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Event Free Survival (EFS)	0.6255 Probability Interval 0.5575 to 0.6934	0.5874 Probability Interval 0.5178 to 0.6569	—

PRIMARY outcome

Timeframe: Reporting Period 1 (Weeks 1 - 15)

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 baseline; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=226 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Response Rate (RR)	0.6667 Proportion Interval 0.6047 to 0.7287	0.6726 Proportion Interval 0.6114 to 0.7337	—

PRIMARY outcome

Timeframe: 4 years

Probability of being alive after 4 years in the study.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=226 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Overall Survival (OS)	0.7293 Probability Interval 0.6669 to 0.7917	0.7223 Probability Interval 0.6583 to 0.7862	—

SECONDARY outcome

Timeframe: 4 years

Population: 17 ineligible participants were excluded.

Compare 4-year EFS using eligible participants only to the historical rate of 0.65 with IRSI-V. The 4-year EFS is probability of no relapse, secondary malignancy, or death after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.65.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison	0.6255 Probability Interval 0.5575 to 0.6934	—	—

SECONDARY outcome

Timeframe: 2 years

Population: 17 ineligible participants were excluded.

Compare 2-year local failure rate to the historical rate of 0.13 with IRSI-V. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.13.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Local Failure	0.1757 Proportion of participants Interval 0.1256 to 0.2257	—	—

SECONDARY outcome

Timeframe: 4 years

Population: 17 ineligible participants were excluded.

Compare 4-year OS using eligible participants only to the historical rate of 0.70 with IRSI-V. The 4-year OS is probability of being alive after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.70.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison	0.7293 Probability Interval 0.6669 to 0.7917	—	—

SECONDARY outcome

Timeframe: Up to 15 weeks

Grade 3 or 4 nausea, diarrhea, dehydration, radiation dermatitis, mucositis due to radiation. Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=226 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Incidence of Toxicity	0.2072 Probability Interval 0.1539 to 0.2605	0.3673 Probability Interval 0.3044 to 0.4301	—

SECONDARY outcome

Timeframe: Up to 43 weeks

Population: Number of patients with specific adverse events.

The toxicity rates will be estimated for each phase and course of treatment, and will be compared to the fixed rates under D9803 using one-sided lower confidence intervals for a single proportion without adjustment for multiple comparisons.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=193 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC Anemia	58 participants	54 participants	—
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC Febrile Neutropenia	30 participants	17 participants	—
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC Nausea or Hepatopathy	6 participants	1 participants	—
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC Platelet Count Decreased	27 participants	63 participants	—
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC Vomiting	9 participants	2 participants	—

SECONDARY outcome

Timeframe: 4 years

Population: 452 participants were excluded due to ineligibility or absence of SUVmax evaluation at baseline and week 4.

4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study).

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=7 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=22 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4	0.2857 Probability Interval 0.0 to 0.6204	0.6364 Probability Interval 0.4354 to 0.8374	—

SECONDARY outcome

Timeframe: 4 years

Population: 421 participants were excluded due to ineligibility or absence of SUVmax evaluation at baseline and week 15.

4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study)

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=9 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=51 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15	0.6667 Probability Interval 0.2895 to 1.0	0.5686 Probability Interval 0.4303 to 0.707	—

SECONDARY outcome

Timeframe: Weeks 4-9 (the first exposure to VI)

Population: Ineligible patients are excluded. Only patients tested for the UGT1A1 genotypes are reported and included in this analysis.

Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=49 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=65 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7 n=12 Participants
Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype Neutropenia, with or without Fever	16 Counts	22 Counts	4 Counts
Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype Diarrhea	5 Counts	14 Counts	5 Counts

SECONDARY outcome

Timeframe: During the study

Population: The analysis was abandoned due to low incidence of toxicity. Data were not collected.

Incidence of toxicity related to VAC treatment in patients with CYP2B6 genotypes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: During the study

Population: The analysis was abandoned due to low incidence of toxicity. Data were not collected.

Incidence of toxicity related to VAC treatment in patients with GSTA1 and CYP2C9 genotypes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 years

Population: Only eligible patients who were tested for their fusion status and PAX partners.

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=88 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=21 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Event Free Survival (EFS) by PAX Status	0.51 Probability Interval 0.39 to 0.64	0.66 Probability Interval 0.37 to 0.94	—

SECONDARY outcome

Timeframe: 3-6 years after enrollment

Population: 470 participants were excluded due to ineligibility or absence of the dysfunctional voiding and incontinence symptoms questionnaire.

Number of patients with a summary score greater than 8.5

Outcome measures

Outcome measures
Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=7 Participants Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With Vincristine, Irinotecan (VI) n=4 Participants Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13,16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.	UGT1A1 Genotype 7/7
Incidence of Bladder Dysfunction	2 Participant	1 Participant	—

Adverse Events

Vincristine, Dactinomycin, Cyclophosphamide (VAC)

Serious events: 4 serious events

Other events: 209 other events

Deaths: 0 deaths

VAC Alternating With VI

Serious events: 11 serious events

Other events: 213 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 Must obtain prior Sponsor approval.
Publication restrictions are in place

Restriction type: OTHER

Measure	Vincristine, Dactinomycin, Cyclophosphamide (VAC) n=222 participants at risk Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies	VAC Alternating With VI n=226 participants at risk Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4. Irinotecan Hydrochloride: Given IV Dactinomycin: Given IV Cyclophosphamide: Given IV Vincristine Sulfate: Given IV Radiation Therapy: Undergo radiotherapy Laboratory Biomarker Analysis: Correlative studies Questionnaire Administration: Ancillary studies
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Hepatobiliary disorders Hepatic pain	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Metabolism and nutrition disorders Hyponatremia	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Nervous system disorders Intracranial hemorrhage	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Investigations Lymphocyte count decreased	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Gastrointestinal disorders Mucositis oral	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.88% 2/226 • Number of events 2 All eligible patients were considered in the evaluation of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Nervous system disorders Nervous system disorders - Other, specify	1.4% 3/222 • Number of events 3 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Gastrointestinal disorders Oral pain	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngeal mucositis	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Investigations Platelet count decreased	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Injury, poisoning and procedural complications Radiation recall reaction (dermatologic)	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Infections and infestations Sepsis	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Injury, poisoning and procedural complications Tracheal obstruction	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Gastrointestinal disorders Esophagitis	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Gastrointestinal disorders Gastritis	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.
Investigations Alanine aminotransferase increased	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Blood and lymphatic system disorders Anemia	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Gastrointestinal disorders Ascites	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Investigations Aspartate aminotransferase increased	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
Investigations Blood bilirubin increased	0.45% 1/222 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.	0.00% 0/226 All eligible patients were considered in the evaluation of adverse events.
General disorders Death NOS	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.88% 2/226 • Number of events 2 All eligible patients were considered in the evaluation of adverse events.
Nervous system disorders Encephalopathy	0.00% 0/222 All eligible patients were considered in the evaluation of adverse events.	0.44% 1/226 • Number of events 1 All eligible patients were considered in the evaluation of adverse events.