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 |
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Recruitment Status :
Completed
First Posted : January 12, 2004
Results First Posted : April 11, 2014
Last Update Posted : November 19, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult Rhabdomyosarcoma Embryonal Childhood Rhabdomyosarcoma Embryonal-botryoid Childhood Rhabdomyosarcoma Previously Untreated Childhood Rhabdomyosarcoma | Procedure: conventional surgery Drug: dactinomycin Drug: cyclophosphamide Drug: vincristine sulfate Radiation: radiation therapy | Phase 3 |
PRIMARY OBJECTIVES:
I. Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine (V), dactinomycin (A), cyclophosphamide (C), and radiotherapy.
SECONDARY OBJECTIVES:
I. Determine local control rates in patients treated with this regimen. II. Determine the rate of second-look surgery in patients with bulk residual tumor at diagnosis (clinical group III) and the proportion of second-look surgeries that render patients treated with this regimen tumor-free or with microscopic tumor only and evaluate the pathologic significance of that residual tumor.
III. Determine the local control rates in patients with clinical group III disease treated with response-adjusted radiotherapy doses after second-look surgical resection.
OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment regimens according to disease stage and clinical group.
REGIMEN I (subset 1 patients) [closed to accrual as of 08/13/2010: Patients receive VAC chemotherapy comprising vincristine 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 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; and radiotherapy**, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose.
REGIMEN II (subset 2 patients)[closed to accrual as of 9/23/2011]: Patients receive VAC chemotherapy and radiotherapy** as in regimen I and VA chemotherapy comprising vincristine 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. Patients with clinical group III disease may undergo second-look surgery at week 13 followed by response-adjusted radiotherapy, and continued VA* chemotherapy. In both regimens, treatment continues in the absence of disease progression or unacceptable toxicity.
NOTE: *For both regimens, dactinomycin is omitted during radiotherapy.
NOTE: **Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodes who have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week 13
Patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 390 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Vincristine, Dactinomycin, and Lower Doses of Cyclophosphamide With or Without Radiation Therapy for Patients With Newly Diagnosed Low-Risk Embryonal/Botryoid/Spindle Cell Rhabdomyosarcoma |
| Study Start Date : | September 4, 2004 |
| Actual Primary Completion Date : | August 13, 2012 |
| Actual Study Completion Date : | September 30, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Regimen I (chemotherapy, radiotherapy)
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)
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Drug: dactinomycin
Given IV
Other Names:
Drug: cyclophosphamide Given IV
Other Names:
Drug: vincristine sulfate Given IV
Other Names:
Radiation: radiation therapy Undergo radiotherapy
Other Names:
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Experimental: Regimen II (chemotherapy, radiotherapy, surgery)
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).
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Procedure: conventional surgery
Some patients may undergo second-look surgery
Other Name: surgery, conventional Drug: dactinomycin Given IV
Other Names:
Drug: cyclophosphamide Given IV
Other Names:
Drug: vincristine sulfate Given IV
Other Names:
Radiation: radiation therapy Undergo radiotherapy
Other Names:
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- Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 1 Failure Free at 5 Years Following Study Entry [ Time Frame: From enrollment up to 5 years ]Kaplan Meier estimate of failure free survival at 5 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first.
- Percentage of Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Failure Free at 5 Years Following Study Entry [ Time Frame: From enrollment up to 5 years ]Kaplan Meier estimate of failure free survival at 5 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first.
- Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 2 Failure Free at 5 Years Following Study Entry [ Time Frame: From enrollment up to 5 years ]Kaplan Meier estimate of failure free survival at 5 years, where failure free survival is defined as the time to relapse, progression, second malignancy, and death whichever occurs first.
- Cumulative Incidence of Patients Who Receive Reduced Doses of Radiation Therapy [ Time Frame: From enrollment up to 5 years ]The local failure rate will be estimated using cumulative incidence curves.
- Percentage of Patients With Delayed Surgical Procedures [ Time Frame: At 13 weeks after induction ]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.
- Cumulative Incidence of Group III Patients Who Received With Reduced Radiotherapy Dose [ Time Frame: From enrollment up to 20 weeks ]The local failure rate will be estimated using cumulative incidence curves for Group III patients who received reduced doses of radiation therapy after second look surgical resection.
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| Ages Eligible for Study: | up to 49 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:
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Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):
- Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
- Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
- Stage 2 and clinical group I or II disease
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Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):
- Stage 1 and clinical group III disease arising in a non-orbit site
- Stage 3 and clinical group I or II disease
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Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)
- If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
- Prior regional lymph node sampling required for patients with extremity tumors
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None of the following diagnoses:
- Intermediate-risk embryonal RMS
- Metastatic embryonal RMS
- Alveolar RMS
- Undifferentiated sarcoma
- RMS not otherwise specified (NOS)
- Other soft tissue sarcoma, including sarcoma NOS
- Prior enrollment on clinical trial COG-D9902
- Performance status - ECOG 0-2
- Performance status - Karnofsky 50-100% (≥ 16 years old)
- Performance status - Lansky 50-100% (< 16 years old)
- Absolute neutrophil count at least 750/mm^3
- Platelet count at least 75,000/mm^3 (transfusion independent)
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)*
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Creatinine* based on age/gender as follows:
- No greater than 0.8 mg/dL for patients age 5 and under
- No greater than 1.0 mg/dL for patients age 6 to 9
- No greater than 1.2 mg/dL for patients age 10 to 12
- No greater than 1.4 mg/dL for female patients age 13 and over
- No greater than 1.5 mg/dL for male patients age 13 to 15
- No greater than 1.7 mg/dL for male patients age 16 and over
- Creatinine clearance* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m^2
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infection
- No prior chemotherapy (except for patients treated on the related intermediate-risk study)
- Prior steroids allowed
- No prior radiotherapy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00075582
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| Principal Investigator: | David Walterhouse, MD | Children's Oncology Group |
Publications:
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00075582 |
| 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 Posted: | January 12, 2004 Key Record Dates |
| Results First Posted: | April 11, 2014 |
| Last Update Posted: | November 19, 2021 |
| Last Verified: | November 2021 |
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Rhabdomyosarcoma Rhabdomyosarcoma, Embryonal Myosarcoma Neoplasms, Muscle Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Sarcoma Dactinomycin Cactinomycin Cyclophosphamide Vincristine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Protein Synthesis Inhibitors Enzyme Inhibitors |