- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00003958
Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma
Randomized Study of Vincristine, Actinomycin-D, and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine, Topotecan and Cyclophosphamide for Patients With Intermediate Risk Rhabdomyosarcoma
Study Overview
Status
Conditions
- Stage III Adult Soft Tissue Sarcoma
- Stage I Adult Soft Tissue Sarcoma
- Stage II Adult Soft Tissue Sarcoma
- Adult Rhabdomyosarcoma
- Adult Malignant Mesenchymoma
- Alveolar Childhood Rhabdomyosarcoma
- Embryonal Childhood Rhabdomyosarcoma
- Embryonal-botryoid Childhood Rhabdomyosarcoma
- Previously Untreated Childhood Rhabdomyosarcoma
- Childhood Malignant Mesenchymoma
- Nonmetastatic Childhood Soft Tissue Sarcoma
Detailed Description
OBJECTIVES:
I. Compare the early response rates, failure-free survival, and survival of patients with intermediate-risk rhabdomyosarcoma treated with surgery, radiotherapy, and vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine, topotecan, and cyclophosphamide.
II. Compare the acute and late effects of these two treatment regimens in these patients.
III. Determine the rate of second-look surgery in selected patients with bulk residual tumor at diagnosis (i.e., Clinical Group III) and the proportion of these that render the patient tumor free or with microscopic tumor only.
IV. Determine the rate of local failure in selected patients with bulk residual tumors at diagnosis (i.e., Clinical Group III) who, after second-look resection, have response-adjusted radiotherapy dose reduction.
V. Determine if preoperative radiotherapy followed by second-look surgery is feasible for selected patients with bulk residual disease (i.e., Clinical Group III) who respond poorly to induction chemotherapy.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease (embryonal histology, stage II or III, Clinical Group III vs embryonal histology, Clinical Group IV, less than 10 years of age vs alveolar or undifferentiated sarcoma histology, stage I, Clinical Group I vs alveolar or undifferentiated sarcoma histology, stage II or III, Clinical Group II or III). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive vincristine IV over 5-10 minutes once a week on weeks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV is administered over 15-20 minutes once a week on weeks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV is administered over 30-60 minutes once a week on weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After the initial 12 weeks of chemotherapy, depending on tumor shrinkage, patients may undergo surgery. After recovery from surgery, patients receive radiotherapy once a day, 5 days a week, during weeks 12-18. For patients receiving radiotherapy during weeks 0-6, dactinomycin is omitted during weeks 3 and 6 and administered during weeks 15 and 18. For patients receiving radiotherapy during weeks 12-18, dactinomycin is omitted during weeks 15 and 18. Patients showing an adequate response at week 24 continue chemotherapy during weeks 24-39.
Patients with Clinical Group III tumors of a parameningeal site with documented evidence of intracranial extension receive radiotherapy within the first 2 weeks of the initiation of the first course of chemotherapy (day 0).
Patients with Clinical Group II parameningeal tumors and Clinical Group III parameningeal tumors with base of skull erosion and/or cranial nerve palsy without evidence of intracranial extension receive radiotherapy on week 12 (day 84) or immediately thereafter.
Patients with Clinical Group IV parameningeal tumors with distant metastases receive radiotherapy to the primary site on week 12 (day 84). Patients with distant metastases confined to one site may receive radiotherapy to the metastatic site concurrently with therapy to the primary site if it began within 2 weeks of the initiation of chemotherapy (day 0).
Arm II: Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39.
All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.
Patients are followed every 1-2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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California
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Arcadia, California, United States, 91006-3776
- Children's Oncology Group
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically proven disease of any of the following types:
Non metastatic alveolar rhabdomyosarcoma
- Stage I, II, or III; Clinical Group I, II, or III
Stage II or III, Clinical Group III embryonal rhabdomyosarcoma
- Botryoid
- Spindle cell
Under 10 years, stage IV, Clinical Group IV embryonal rhabdomyosarcoma
- Botryoid
- Spindle cell
Undifferentiated sarcoma
- Stage I, II, or III; Clinical Group I, II, or III
Ectomesenchymoma
- Stage I, II, or III; Clinical Group I, II, or III, with alveolar features
- Under 10 years, Stage IV, Clinical Group IV, with embryonal features
- No more than 6 weeks since initial surgical procedure (e.g., biopsy) giving the definitive diagnosis
- No parameningeal rhabdomyosarcoma with positive CSF cytology or multiple intracranial metastases
- Bilirubin no greater than 1.5 mg/dL
- Creatinine normal* for age
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No prior chemotherapy
- Prior steroids allowed
- No prior radiotherapy
- See Disease Characteristics
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I
Vincristine sulfate IV once a wk on wks 0-12, 15, 18-24, 27, 30-36, and 39.
Dactinomycin IV once a wk on wks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39.
Cyclophosphamide IV once a wk on wks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39.
After 12 weeks of chemotherapy, depending on tumor shrinkage, pts may undergo surgery.
After recovery from therapeutic conventional surgery, patients receive radiation therapy once a day, 5 days a wk, during wks 12-18.
For pt receiving radiotherapy during wks 0-6, dactinomycin is omitted during wks 3 and 6 and during wks 15 and 18.
For patients receiving radiotherapy during wks 12-18, dactinomycin is omitted during wks 15 and 18. Patients with adequate response at wk 24 continue chemotherapy during wks 24-39.
All pts receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.
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Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Undergo radiotherapy
Other Names:
Undergo surgery
Given SC
Other Names:
Given IV
Other Names:
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Experimental: Arm II
Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan hydrochloride IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery. |
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Undergo radiotherapy
Other Names:
Undergo surgery
Given SC
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Long-term failure-free survival (FFS) between the two treatment groups
Time Frame: Up to 5 years
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Up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival between treatments
Time Frame: Up to 5 years
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Up to 5 years
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Rate of second look surgery
Time Frame: Week 12
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Week 12
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Proportion of patients rendered tumor-free or with microscopic tumor only
Time Frame: Week 12
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Week 12
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Estimation of the rate of local failure for the patients who undergo second look surgery
Time Frame: Week 12
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Done using standard cumulative incidence curves.
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Week 12
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Carola Arndt, Children's Oncology Group
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Complex and Mixed
- Neoplasms, Muscle Tissue
- Myosarcoma
- Sarcoma
- Rhabdomyosarcoma
- Rhabdomyosarcoma, Embryonal
- Mesenchymoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Protein Synthesis Inhibitors
- Antibiotics, Antineoplastic
- Topoisomerase I Inhibitors
- Cyclophosphamide
- Vincristine
- Topotecan
- Sargramostim
- Dactinomycin
- Cactinomycin
Other Study ID Numbers
- D9803
- U10CA098543 (U.S. NIH Grant/Contract)
- NCI-2012-02302 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- IRS-D9803 (Other Identifier: Intergroup Rhabdosarcoma Group)
- COG-D9803 (Other Identifier: Children's Oncology Group)
- POG-D9803 (Other Identifier: Pediatric Oncology Group)
- CDR0000067157 (Other Identifier: Clinical Trials.gov)
- CCG-D9803 (Other Identifier: Children's Cancer Group)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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