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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00354835




Registration number
NCT00354835
Ethics application status
Date submitted
19/07/2006
Date registered
20/07/2006
Date last updated
31/01/2023

Titles & IDs
Public title
Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
Scientific title
Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)
Secondary ID [1] 0 0
NCI-2009-00427
Secondary ID [2] 0 0
ARST0531
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Rhabdomyosarcoma 0 0
Childhood Alveolar Rhabdomyosarcoma 0 0
Childhood Botryoid-Type Embryonal Rhabdomyosarcoma 0 0
Childhood Embryonal Rhabdomyosarcoma 0 0
Localized Childhood Soft Tissue Sarcoma 0 0
Rhabdomyosarcoma 0 0
Sarcoma 0 0
Stage I Adult Soft Tissue Sarcoma AJCC v7 0 0
Stage II Adult Soft Tissue Sarcoma AJCC v7 0 0
Stage III Adult Soft Tissue Sarcoma AJCC v7 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Other interventions - Dactinomycin
Treatment: Drugs - Irinotecan Hydrochloride
Other interventions - Laboratory Biomarker Analysis
Other interventions - Questionnaire Administration
Treatment: Other - Radiation Therapy
Treatment: Drugs - Vincristine Sulfate

Active Comparator: Arm I (chemotherapy, radiotherapy) - 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.

Experimental: Arm II (chemotherapy, radiotherapy) - 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.


Treatment: Drugs: Cyclophosphamide
Given IV

Other interventions: Dactinomycin
Given IV

Treatment: Drugs: Irinotecan Hydrochloride
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Other: Radiation Therapy
Undergo radiotherapy

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival (EFS)
Timepoint [1] 0 0
4 years
Primary outcome [2] 0 0
Response Rate (RR)
Timepoint [2] 0 0
Reporting Period 1 (Weeks 1 - 15)
Primary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
4 years
Secondary outcome [1] 0 0
Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
Local Failure
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison
Timepoint [3] 0 0
4 years
Secondary outcome [4] 0 0
Incidence of Toxicity
Timepoint [4] 0 0
Up to 15 weeks
Secondary outcome [5] 0 0
Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC
Timepoint [5] 0 0
Up to 43 weeks
Secondary outcome [6] 0 0
Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4
Timepoint [6] 0 0
4 years
Secondary outcome [7] 0 0
Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15
Timepoint [7] 0 0
4 years
Secondary outcome [8] 0 0
Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype
Timepoint [8] 0 0
Weeks 4-9 (the first exposure to VI)
Secondary outcome [9] 0 0
Toxicity With CYP2B6 Genotypes
Timepoint [9] 0 0
During the study
Secondary outcome [10] 0 0
Toxicity With GSTA1 and CYP2C9 Genotypes
Timepoint [10] 0 0
During the study
Secondary outcome [11] 0 0
Event Free Survival (EFS) by PAX Status
Timepoint [11] 0 0
4 years
Secondary outcome [12] 0 0
Incidence of Bladder Dysfunction
Timepoint [12] 0 0
3-6 years after enrollment

Eligibility
Key inclusion criteria
- Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of
embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study

- Enrollment on COG-D9902 to confirm local histologic diagnosis with central pathology
review is required for all patients

- Patients may be enrolled on ARST0531 and start protocol treatment prior to receipt of
central pathology review results

- Patient must have Intermediate-risk RMS defined as:

- Embryonal, botryoid, or spindle cell RMS, or ectomesenchymoma: stage 2 or 3 and
group III OR

- Alveolar RMS: stage 1-3 and group I-III

- Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) is required for all
patients >= 10 years of age with paratesticular tumors and for patients < 10 years
with clinically or radiographically involved lymph nodes (except when extensive lymph
node involvement, defined as two or more lymph nodes > 2 cm in dimension, is
identified by imaging studies)

- Regional lymph node sampling or sentinel lymph node procedure is required for
histologic evaluation in patients with extremity tumors

- Clinically or radiographically enlarged nodes should be sampled for histologic
evaluation

- Detection of metastasis by optional FDG PET (not required for study enrollment); FDG
PET may detect abnormalities suggestive of metastasis not identified by bone scan,
computed tomography (CT), or bone marrow aspiration/biopsy; the prognostic
significance of FDG PET-detected abnormalities is not clear; FDG PET-detected
abnormalities MUST be confirmed to be metastases by an additional imaging modality
(such as magnetic resonance imaging [MRI] or CT) OR pathologic confirmation; unless
FDG PET abnormalities are confirmed by another imaging modality or biopsy, FDG PET
abnormalities will NOT be considered evidence of metastasis

- Patients must have a performance status of 0, 1, or 2; the Lansky performance score
should be used for patients < 16 years and the Karnofsky performance score for
patients >= 16 years

- Patients who have received prior chemotherapy (excluding steroids) or radiation
therapy, except for patients transferring from ARST0331 (low-risk study), are not
eligible

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

- 1 month to < 6 months: 0.4 mg/dL

- 6 months to < 1 year: 0.5 mg/dL

- 1 to < 2 years: 0.6 mg/dL

- 2 to < 6 years: 0.8 mgt/dL

- 6 to < 10 years: 1 mg/dL

- 10 to < 13 years: 1.2 mg/dL

- 13 to < 16 years: 1.5 mg/dL (males) or 1.4 mg/dL (females)

- >= 16 years: 1.7 mg/dL (males) or 1.4 mg/dL (females)

- Patients with urinary tract obstruction by tumor must meet the renal function criteria
AND must have unimpeded urinary flow established via decompression of the obstructed
portion of the urinary tract

- Total bilirubin =< 1.5 x upper limit of normal for age

- Peripheral absolute neutrophil count (ANC) >= 750/uL

- Platelet count >= 75,000/uL (transfusion independent)

- No evidence of uncontrolled infection

- Patients must be able to undergo radiation therapy, if necessary, as specified in the
protocol

- Female patients of childbearing potential must have a negative pregnancy test

- Female patients who are breast feeding must agree to stop breast feeding

- Sexually active patients of childbearing potential must be willing to use effective
contraception during therapy and for at least 1 month after treatment is completed

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Minimum age
No limit
Maximum age
49 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/12/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2022
Sample size
Target
Accrual to date
Final
481
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [8] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [9] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
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Illinois
Country [14] 0 0
United States of America
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Indiana
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Iowa
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United States of America
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Kentucky
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Louisiana
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Maine
Country [19] 0 0
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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North Dakota
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United States of America
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [48] 0 0
Alberta
Country [49] 0 0
Canada
State/province [49] 0 0
British Columbia
Country [50] 0 0
Canada
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Manitoba
Country [51] 0 0
Canada
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Newfoundland and Labrador
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Canada
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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New Zealand
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Auckland
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Puerto Rico
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San Juan
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Switzerland
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Bern
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Switzerland
State/province [59] 0 0
Geneva

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This randomized phase III trial is studying two different combination chemotherapy regimens
to compare how well they work when given together with radiation therapy in treating patients
with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine
sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways
to stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination
chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known
which combination chemotherapy regimen is more effective when given together with radiation
therapy in treating patients with rhabdomyosarcoma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00354835
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Douglas S Hawkins
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00354835