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Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma

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ClinicalTrials.gov Identifier: NCT00075582
Recruitment Status : Unknown
Verified October 2016 by Children's Oncology Group.
Recruitment status was:  Active, not recruiting
First Posted : January 12, 2004
Results First Posted : April 11, 2014
Last Update Posted : November 4, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Rhabdomyosarcoma
Embryonal Childhood Rhabdomyosarcoma
Embryonal-botryoid Childhood Rhabdomyosarcoma
Previously Untreated Childhood Rhabdomyosarcoma
Interventions Procedure: conventional surgery
Drug: dactinomycin
Drug: cyclophosphamide
Drug: vincristine sulfate
Radiation: radiation therapy
Enrollment 390
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery)
Hide Arm/Group Description

Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).

conventional surgery: Some patients may undergo second-look surgery

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Period Title: Overall Study
Started 305 85
Completed 255 50
Not Completed 50 35
Reason Not Completed
Adverse Event             3             1
Lack of Efficacy             4             8
Physician Decision             5             8
Withdrawal by Subject             2             2
Ineligible for study             36             16
Arm/Group Title Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery) Total
Hide Arm/Group Description

Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).

conventional surgery: Some patients may undergo second-look surgery

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Total of all reporting groups
Overall Number of Baseline Participants 305 85 390
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 305 participants 85 participants 390 participants
7.69  (5.81) 5.02  (6.78) 7.11  (6.13)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 305 participants 85 participants 390 participants
Female
88
  28.9%
55
  64.7%
143
  36.7%
Male
217
  71.1%
30
  35.3%
247
  63.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 305 participants 85 participants 390 participants
American Indian or Alaska Native
2
   0.7%
2
   2.4%
4
   1.0%
Asian
9
   3.0%
2
   2.4%
11
   2.8%
Native Hawaiian or Other Pacific Islander
1
   0.3%
0
   0.0%
1
   0.3%
Black or African American
39
  12.8%
9
  10.6%
48
  12.3%
White
228
  74.8%
65
  76.5%
293
  75.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
26
   8.5%
7
   8.2%
33
   8.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 305 participants 85 participants 390 participants
Hispanic or Latino
38
  12.5%
9
  10.6%
47
  12.1%
Not Hispanic or Latino
255
  83.6%
71
  83.5%
326
  83.6%
Unknown or Not Reported
12
   3.9%
5
   5.9%
17
   4.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 305 participants 85 participants 390 participants
United States 269 77 346
Canada 21 5 26
Australia 7 3 10
Netherlands 2 0 2
New Zealand 1 0 1
Puerto Rico 2 0 2
Switzerland 3 0 3
1.Primary Outcome
Title Estimated Percentage of Patients Failure Free at 5 Years (95% Confidence Interval)
Hide Description Failure-free survival: Time to disease recurrence or death as a first event. An analysis plan based on the method of Woolson (1981) will be used to monitor outcome for these patients.
Time Frame 5 years from study enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
Arm/Group Title Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery)
Hide Arm/Group Description:

Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).

conventional surgery: Some patients may undergo second-look surgery

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Overall Number of Participants Analyzed 269 69
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated percentage of participants
87
(82 to 91)
67
(52 to 79)
2.Primary Outcome
Title Estimated Percentage of Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Group I or Stage 2 Group II Disease Treated With Regimen 1 Failure-free at 5 Years
Hide Description Failure-free survival: Time to disease recurrence or death as a first event. An analysis plan based on the method of Woolson (1981) will be used to monitor outcome for these patients.
Time Frame 5 years from study enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All eligible patients among this subset of regimen 1 patients were included in this outcome measure restricted to regimen 1 patients (there were 36 patients determined ineligible). Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome measures.
Arm/Group Title Regimen I (Chemotherapy, Radiotherapy)
Hide Arm/Group Description:

Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Overall Number of Participants Analyzed 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated percentage of participants
90
(72 to 97)
3.Primary Outcome
Title Estimated Percentage of Patients With Low-risk Rhabdomyosarcoma Treated With Regimen 2 Therapy Failure Free at 5 Years (95% Confidence Interval).
Hide Description Failure free survival: Time to disease recurrence or death as a first event. An analysis plan based on the method of Woolson (1981) will be used to monitor outcome for these patients.
Time Frame 5 years from study enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All eligible patients among this subset of regimen 2 patients were included in this outcome measure to regimen 2 patients (there were 16 patients determined ineligible). Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome measures.
Arm/Group Title Regimen II (Chemotherapy, Radiotherapy, Surgery)
Hide Arm/Group Description:

Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).

conventional surgery: Some patients may undergo second-look surgery

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Overall Number of Participants Analyzed 69
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated percentage of participants
67
(52 to 79)
4.Secondary Outcome
Title Rate of Local Failure for Patients Who Receive Reduced Doses of Radiation Therapy
Hide Description The local failure rate will be estimated using cumulative incidence curves.
Time Frame Up to 10 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Rate of Second-look Surgery and the Proportion of Patients Who Are Tumor-free or With Microscopic Tumor Only Following Second-look Surgeries
Hide Description The decision to perform second-look surgery should be based on the physical examination and imaging studies at Week 12 and should only be considered if a reasonable functional and cosmetic result is anticipated.
Time Frame At 13 weeks
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Rate of Local Failure for Patients With Clinical Group III Disease When the Radiotherapy Dose is Reduced After Second-look Surgical Resection.
Hide Description The local failure rate will be estimated using cumulative incidence curves.
Time Frame Up to 20 weeks
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome.
 
Arm/Group Title Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery)
Hide Arm/Group Description

Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).

conventional surgery: Some patients may undergo second-look surgery

dactinomycin: Given IV

cyclophosphamide: Given IV

vincristine sulfate: Given IV

radiation therapy: Undergo radiotherapy

All-Cause Mortality
Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/272 (0.37%)      1/70 (1.43%)    
Investigations     
Neutrophil count decreased  0/272 (0.00%)  1/70 (1.43%)  1
White blood cell decreased  1/272 (0.37%)  1 0/70 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Regimen I (Chemotherapy, Radiotherapy) Regimen II (Chemotherapy, Radiotherapy, Surgery)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   74/272 (27.21%)      27/70 (38.57%)    
Blood and lymphatic system disorders     
Anemia  14/272 (5.15%)  14 9/70 (12.86%)  9
Disseminated intravascular coagulation  1/272 (0.37%)  1 0/70 (0.00%) 
Febrile neutropenia  14/272 (5.15%)  14 7/70 (10.00%)  7
Cardiac disorders     
Sinus tachycardia  1/272 (0.37%)  1 0/70 (0.00%) 
Eye disorders     
Photophobia  1/272 (0.37%)  1 0/70 (0.00%) 
Watering eyes  1/272 (0.37%)  1 0/70 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  2/272 (0.74%)  2 1/70 (1.43%)  1
Constipation  3/272 (1.10%)  3 1/70 (1.43%)  1
Diarrhea  1/272 (0.37%)  1 0/70 (0.00%) 
Flatulence  1/272 (0.37%)  1 0/70 (0.00%) 
Ileus  1/272 (0.37%)  1 0/70 (0.00%) 
Mucositis oral  2/272 (0.74%)  2 2/70 (2.86%)  2
Nausea  3/272 (1.10%)  3 0/70 (0.00%) 
Oral pain  1/272 (0.37%)  1 0/70 (0.00%) 
Small intestinal obstruction  0/272 (0.00%)  1/70 (1.43%)  1
Vomiting  5/272 (1.84%)  5 0/70 (0.00%) 
General disorders     
Facial pain  1/272 (0.37%)  1 0/70 (0.00%) 
Fatigue  1/272 (0.37%)  1 0/70 (0.00%) 
Fever  5/272 (1.84%)  5 4/70 (5.71%)  4
Non-cardiac chest pain  1/272 (0.37%)  1 0/70 (0.00%)  0
Pain  2/272 (0.74%)  2 1/70 (1.43%)  1
Hepatobiliary disorders     
Hepatobiliary disorders - Other  2/272 (0.74%)  2 0/70 (0.00%)  0
Infections and infestations     
Catheter related infection  2/272 (0.74%)  2 1/70 (1.43%)  1
Conjunctivitis infective  1/272 (0.37%)  1 0/70 (0.00%)  0
Infections and infestations - Other  4/272 (1.47%)  4 5/70 (7.14%)  5
Rhinitis infective  1/272 (0.37%)  1 0/70 (0.00%)  0
Upper respiratory infection  1/272 (0.37%)  1 0/70 (0.00%)  0
Urinary tract infection  2/272 (0.74%)  2 2/70 (2.86%)  2
Injury, poisoning and procedural complications     
Dermatitis radiation  1/272 (0.37%)  1 0/70 (0.00%)  0
Investigations     
Alanine aminotransferase increased  9/272 (3.31%)  9 2/70 (2.86%)  2
Alkaline phosphatase increased  0/272 (0.00%)  0 1/70 (1.43%)  1
Aspartate aminotransferase increased  7/272 (2.57%)  7 3/70 (4.29%)  3
Blood bilirubin increased  2/272 (0.74%)  2 0/70 (0.00%) 
Creatinine increased  1/272 (0.37%)  1 1/70 (1.43%)  1
Lymphocyte count decreased  2/272 (0.74%)  2 3/70 (4.29%)  3
Neutrophil count decreased  43/272 (15.81%)  43 15/70 (21.43%)  15
Platelet count decreased  10/272 (3.68%)  10 1/70 (1.43%)  1
Weight loss  2/272 (0.74%)  2 3/70 (4.29%)  3
White blood cell decreased  23/272 (8.46%)  23 10/70 (14.29%)  10
Metabolism and nutrition disorders     
Anorexia  0/272 (0.00%)  0 1/70 (1.43%)  1
Hypercalcemia  1/272 (0.37%)  1 0/70 (0.00%) 
Hyperglycemia  4/272 (1.47%)  4 4/70 (5.71%)  4
Hyperkalemia  0/272 (0.00%)  1/70 (1.43%)  1
Hypoalbuminemia  1/272 (0.37%)  1 0/70 (0.00%) 
Hypocalcemia  1/272 (0.37%)  1 0/70 (0.00%) 
Hypokalemia  1/272 (0.37%)  1 1/70 (1.43%)  1
Hyponatremia  1/272 (0.37%)  1 0/70 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle weakness upper limb  1/272 (0.37%)  1 0/70 (0.00%) 
Neck pain  1/272 (0.37%)  1 0/70 (0.00%) 
Nervous system disorders     
Headache  1/272 (0.37%)  1 0/70 (0.00%) 
Peripheral motor neuropathy  4/272 (1.47%)  4 1/70 (1.43%)  1
Peripheral sensory neuropathy  4/272 (1.47%)  4 1/70 (1.43%)  1
Pyramidal tract syndrome  1/272 (0.37%)  1 0/70 (0.00%) 
Reproductive system and breast disorders     
Scrotal pain  1/272 (0.37%)  1 0/70 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  0/272 (0.00%)  1/70 (1.43%)  1
Skin and subcutaneous tissue disorders     
Alopecia  1/272 (0.37%)  1 0/70 (0.00%) 
Skin and subcutaneous tissue disorders - Other, specify  3/272 (1.10%)  3 0/70 (0.00%) 
Skin hyperpigmentation  2/272 (0.74%)  2 0/70 (0.00%) 
Skin hypopigmentation  1/272 (0.37%)  1 0/70 (0.00%) 
Vascular disorders     
Vascular disorders - Other  0/272 (0.00%)  1/70 (1.43%)  1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
Publications:
Woolson RF (1981) Rank-tests and a one-sample log-rank test for comparing observed survival-data to a standard population. Biometrics 37: 687-696.
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00075582     History of Changes
Other Study ID Numbers: ARST0331
NCI-2009-00425 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-ARST0331 ( Other Identifier: Children's Oncology Group )
CDR0000347078 ( Other Identifier: Clinical Trials.gov )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: January 9, 2004
First Posted: January 12, 2004
Results First Submitted: December 16, 2013
Results First Posted: April 11, 2014
Last Update Posted: November 4, 2016