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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00075582

Purpose

RATIONALE: 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.

PURPOSE: This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma.

Condition	Intervention	Phase
Sarcoma	Biological: dactinomycin Drug: cyclophosphamide Drug: vincristine sulfate Procedure: conventional surgery Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma Surgery

Drug Information available for: Cyclophosphamide Dactinomycin Vincristine Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Failure-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	360
Study Start Date:	September 2004
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen I (subset 1 patients): Experimental 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 (dactinomycin is omitted during radiotherapy); and radiotherapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiotherapy; some start it at week 24.	Biological: dactinomycin Given IV Drug: cyclophosphamide Given IV Drug: vincristine sulfate Given IV Procedure: conventional surgery Some patients may undergo second-look surgery Radiation: radiation therapy Some patients undergo radiotherapy
Regimen II (subset 2 patients): Experimental 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 (dactinomycin is omitted during radiotherapy). Some patients do not receive radiotherapy; some start it at week 24.	Biological: dactinomycin Given IV Drug: cyclophosphamide Given IV Drug: vincristine sulfate Given IV Procedure: conventional surgery Some patients may undergo second-look surgery Radiation: radiation therapy Some patients undergo radiotherapy

Arms

Assigned Interventions

Regimen I (subset 1 patients): Experimental

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 (dactinomycin is omitted during radiotherapy); and radiotherapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiotherapy; some start it at week 24.

Biological: dactinomycin

Given IV

Drug: cyclophosphamide

Given IV

Drug: vincristine sulfate

Given IV

Procedure: conventional surgery

Some patients may undergo second-look surgery

Radiation: radiation therapy

Some patients undergo radiotherapy

Regimen II (subset 2 patients): Experimental

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 (dactinomycin is omitted during radiotherapy). Some patients do not receive radiotherapy; some start it at week 24.

Biological: dactinomycin

Given IV

Drug: cyclophosphamide

Given IV

Drug: vincristine sulfate

Given IV

Procedure: conventional surgery

Some patients may undergo second-look surgery

Radiation: radiation therapy

Some patients undergo radiotherapy

Detailed Description:

OBJECTIVES:

Primary

Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine, dactinomycin, cyclophosphamide, and radiotherapy.

Secondary

Determine local control rates in patients treated with this regimen.
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.
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): 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): 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, administered as in regimen I, and continued VA* chemotherapy as in regimen I or II.

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 every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 360 patients (260 for regimen I [subset 1] and 100 for regimen II [subset 2]) will be accrued for this study within 6 years.

Eligibility

Ages Eligible for Study:	up to 49 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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:
  - 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:
  - 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

PATIENT CHARACTERISTICS:

Age

Under 50
- No infants who would not be able to receive study radiotherapy, in the opinion of the treating physician

Performance status

ECOG 0-2 OR
Karnofsky 50-100% (≥ 16 years old) OR
Lansky 50-100% (< 16 years old)

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 750/mm^3
Platelet count at least 75,000/mm^3 (transfusion independent)

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)* NOTE: *Patients with primary hepatic or biliary tumors and bilirubin greater than 1.5 times ULN allowed provided all other eligibility criteria are met

Renal

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 OR
Creatinine clearance* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m^2 NOTE: *Patients with tumors obstructing the urinary tract causing elevated creatinine allowed provided all other eligibility criteria are met and unimpeded urinary flow is established via decompression of the obstructed portion of the urinary tract

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy (except for patients treated on the related intermediate-risk study)

Endocrine therapy

Prior steroids allowed

Radiotherapy

No prior radiotherapy

Surgery

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075582

Show 185 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	David O. Walterhouse, MD	Children's Memorial Hospital
Investigator:	Alberto S. Pappo, MD	Texas Children's Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Chang HL, Rosenberg AE, Friedmann AM, Ryan DP, Masiakos PT. Primary Pulmonary Rhabdomyosarcoma in a 5-month-old Boy: A Case Report. J Pediatr Hematol Oncol. 2008 Jun;30(6):461-463.

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000347078, COG-ARST0331
Study First Received:	January 9, 2004
Last Updated:	November 24, 2009
ClinicalTrials.gov Identifier:	NCT00075582 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

previously untreated childhood rhabdomyosarcoma
embryonal childhood rhabdomyosarcoma
embryonal-botryoid childhood rhabdomyosarcoma
adult rhabdomyosarcoma

stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage I adult soft tissue sarcoma

Additional relevant MeSH terms:

Neoplasms, Muscle Tissue
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms, Connective and Soft Tissue
Anti-Bacterial Agents
Dactinomycin
Therapeutic Uses
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Rhabdomyosarcoma

Neoplasms by Histologic Type
Myosarcoma
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Immunosuppressive Agents
Pharmacologic Actions
Protein Synthesis Inhibitors
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Sarcoma
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 27, 2009