NCT00075582 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2021-11-19

This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 1 Failure Free at 5 Years Following Study Entry

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outcome · POSTED

Percentage of Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Failure Free at 5 Years Following Study Entry

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outcome · POSTED

Percentage of Patients With Low-risk Rhabdomyosarcoma in Subset 2 Failure Free at 5 Years Following Study Entry

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outcome · POSTED

Cumulative Incidence of Patients Who Receive Reduced Doses of Radiation Therapy

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outcome · POSTED

Percentage of Patients With Delayed Surgical Procedures

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outcome · POSTED

Cumulative Incidence of Group III Patients Who Received With Reduced Radiotherapy Dose

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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: * 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 * 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 * 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 * 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)\* * 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
healthy Volunteers: false
maximum Age: 49 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

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)
intervention Names
Drug: dactinomycin
Drug: cyclophosphamide
Drug: vincristine sulfate
Radiation: radiation therapy
label
Regimen I (chemotherapy, radiotherapy)
type
EXPERIMENTAL
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).
intervention Names
Procedure: conventional surgery
Drug: dactinomycin
Drug: cyclophosphamide
Drug: vincristine sulfate
Radiation: radiation therapy
label
Regimen II (chemotherapy, radiotherapy, surgery)
type
EXPERIMENTAL

interventions

arm Group Labels
Regimen II (chemotherapy, radiotherapy, surgery)
description
Some patients may undergo second-look surgery
name
conventional surgery
other Names
surgery, conventional
type
PROCEDURE
arm Group Labels
Regimen I (chemotherapy, radiotherapy)
Regimen II (chemotherapy, radiotherapy, surgery)
description
Given IV
name
dactinomycin
other Names
ACT-D
actinomycin C1
AD
Cosmegen
DACT
type
DRUG
arm Group Labels
Regimen I (chemotherapy, radiotherapy)
Regimen II (chemotherapy, radiotherapy, surgery)
description
Given IV
name
cyclophosphamide
other Names
CPM
CTX
Cytoxan
Endoxan
Endoxana
type
DRUG
arm Group Labels
Regimen I (chemotherapy, radiotherapy)
Regimen II (chemotherapy, radiotherapy, surgery)
description
Given IV
name
vincristine sulfate
other Names
leurocristine sulfate
VCR
Vincasar PFS
type
DRUG
arm Group Labels
Regimen I (chemotherapy, radiotherapy)
Regimen II (chemotherapy, radiotherapy, surgery)
description
Undergo radiotherapy
name
radiation therapy
other Names
irradiation
radiotherapy
therapy, radiation
type
RADIATION

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 390
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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
description
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.
measure
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
description
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.
measure
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

secondary Outcomes

description
The local failure rate will be estimated using cumulative incidence curves.
measure
Cumulative Incidence of Patients Who Receive Reduced Doses of Radiation Therapy
time Frame
From enrollment up to 5 years
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.
measure
Percentage of Patients With Delayed Surgical Procedures
time Frame
At 13 weeks after induction
description
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.
measure
Cumulative Incidence of Group III Patients Who Received With Reduced Radiotherapy Dose
time Frame
From enrollment up to 20 weeks

Full study description

brief Summary: This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.
detailed Description: 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.

Source references

references

citation
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.
type
BACKGROUND
citation
de Traux de Wardin H, Dermawan JK, Vanoli F, Jiang SC, Singer S, Chi P, Tap W, Wexler LH, Antonescu CR. NF1-Driven Rhabdomyosarcoma Phenotypes: A Comparative Clinical and Molecular Study of NF1-Mutant Rhabdomyosarcoma and NF1-Associated Malignant Triton Tumor. JCO Precis Oncol. 2024 Apr;8:e2300597. doi: 10.1200/PO.23.00597.
pmid
38603649
type
DERIVED
citation
Proia AD. Spindle Cell/Sclerosing Rhabdomyosarcoma of the Orbit. Ophthalmic Plast Reconstr Surg. 2023 Jan-Feb 01;39(1):e17-e20. doi: 10.1097/IOP.0000000000002252. Epub 2022 Jul 13.
pmid
35829629
type
DERIVED