Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00354835

Purpose

RATIONALE: Drugs used in chemotherapy, such as vincristine, dactinomycin, cyclophosphamide, and irinotecan, 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.

PURPOSE: 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.

Condition	Intervention	Phase
Sarcoma	Biological: dactinomycin Drug: cyclophosphamide Drug: irinotecan hydrochloride Drug: vincristine sulfate Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Cyclophosphamide Dactinomycin Vincristine Irinotecan U 101440E Irinotecan hydrochloride Vincristine sulfate

U.S. FDA Resources

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

Primary Outcome Measures:

Early response rate [ Designated as safety issue: No ]
Failure-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Acute and late effects of vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine and irinotecan hydrochloride [ Designated as safety issue: No ]

Estimated Enrollment:	486
Study Start Date:	December 2006
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (VAC): Active Comparator 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.	Biological: dactinomycin Given IV over 1-5 minutes Drug: cyclophosphamide Given IV over 1 hour Drug: vincristine sulfate Given IV over 1 minute Radiation: radiation therapy Given 5 days a week for 4-6 weeks beginning in week 4
Arm II (VAC/VI): Experimental 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.	Biological: dactinomycin Given IV over 1-5 minutes Drug: cyclophosphamide Given IV over 1 hour Drug: irinotecan hydrochloride Given IV over 1 hour Drug: vincristine sulfate Given IV over 1 minute Radiation: radiation therapy Given 5 days a week for 4-6 weeks beginning in week 4

Arms

Assigned Interventions

Arm I (VAC): Active Comparator

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.

Biological: dactinomycin

Given IV over 1-5 minutes

Drug: cyclophosphamide

Given IV over 1 hour

Drug: vincristine sulfate

Given IV over 1 minute

Radiation: radiation therapy

Given 5 days a week for 4-6 weeks beginning in week 4

Arm II (VAC/VI): Experimental

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.

Biological: dactinomycin

Given IV over 1-5 minutes

Drug: cyclophosphamide

Given IV over 1 hour

Drug: irinotecan hydrochloride

Given IV over 1 hour

Drug: vincristine sulfate

Given IV over 1 minute

Radiation: radiation therapy

Given 5 days a week for 4-6 weeks beginning in week 4

Detailed Description:

OBJECTIVES:

Primary

Compare the early response rates in patients with intermediate-risk rhabdomyosarcoma (RMS) treated with vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine and irinotecan hydrochloride (VI) in combination with radiotherapy.
Compare failure-free survival (FFS) and overall survival of patients treated with these regimens.

Secondary

Compare FFS, local control, and survival of patients with intermediate-risk RMS treated with VAC and early (week 4) radiotherapy vs delayed (week 10) radiotherapy, using data from IRS-IV for historic comparison.
Compare the acute and late effects of VAC vs VAC alternating with VI, including the toxicity associated with concurrent VI and radiotherapy.
Compare the acute and late effects of VAC as delivered on this study to that administered on COG-D9803.
Correlate change in fludeoxyglucose F^18 positron emission tomography (FDG-PET) maximum standard uptake value from week 1 to week 4 and 15 with FFS.
Correlate UGT1A1 genotype with VI toxicity in patients receiving VAC alternating with VI.
Correlate CYP2B6, CYP2C9, and GSTA1 genotypes with VAC toxicity.
Prospectively evaluate and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.

OUTLINE: This is a prospective, historic control, randomized, multicenter study. Patients are stratified according to histology, disease stage, and clinical group (group III, stage 2 or 3 embryonal rhabdomyosarcoma [RMS] vs group I, stage 1 alveolar RMS vs group II or III, stage 2 or 3 alveolar RMS). Patients are randomized to 1 of 2 treatment arms. within 42 days of initial surgery or biopsy.

Arm I (VAC): 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.
Arm II (VAC/VI): 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 90 minutes on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients* in both arms also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4 (except patients with alveolar RMS rendered group I by amputation OR patients needing week 1 emergency radiotherapy for symptomatic spinal cord compression).

NOTE: *Individualized local control plan that deviates from protocol-mandated radiotherapy allowed for patients ≤ 24 months of age

After completion of study treatment, patients are followed periodically for ≥ 10 years.

PROJECTED ACCRUAL: A total of 486 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed rhabdomyosarcoma (RMS)
- Must be concurrently enrolled on COG-D9902 to confirm local histologic diagnosis
Intermediate-risk disease, defined by 1 of the following surgicopathologic and staging criteria:
- Group III, stage 2 or 3 embryonal, botryoid, or spindle cell RMS
- Group III, stage 2 or 3 ectomesenchymoma
- Group I-III, stage 1-3 alveolar RMS
Newly diagnosed disease
Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) required for patients ≥ 10 years of age with paratesticular tumors and for patients < 10 years with clinically or radiographically involved lymph nodes
- Patients with extensive lymph node involvement, defined as ≥ 2 lymph nodes > 2 cm in dimension, identified by imaging studies, are not required to undergo SIRLND
Regional lymph node sampling or sentinel lymph node procedure is required for histologic evaluation in patients with extremity tumors
Has undergone initial surgery or biopsy within the past 42 days
Must be able to undergo radiotherapy

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 (Karnofsky PS 50-100% [≥ 16 years of age] or Lansky PS 50-100% [< 16 years of age])
Absolute neutrophil count ≥ 750/mm^3
Platelet count ≥ 75,000/mm^3 (transfusion independent)
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (40 mL/min for infants < 1 year of age)
Patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment
No evidence of uncontrolled infection

PRIOR CONCURRENT THERAPY:

No prior chemotherapy* (excluding steroids)
No prior radiotherapy*
No concurrent aprepitant during treatment with cyclophosphamide NOTE: *Patients who received prior radiotherapy or chemotherapy while enrolled on COG-ARST0331 allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354835

Show 163 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Douglas Hawkins, MD	Seattle Children's Hospital
Investigator:	Geoffrey McCowage, MD	Children's Hospital at Westmead
Investigator:	Leo Mascarenhas, MD	Children's Hospital Los Angeles

More Information

Additional Information:

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

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000487560, COG-ARST0531
Study First Received:	July 19, 2006
Last Updated:	February 6, 2010
ClinicalTrials.gov Identifier:	NCT00354835 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

alveolar childhood rhabdomyosarcoma
embryonal childhood rhabdomyosarcoma
embryonal-botryoid childhood rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
childhood malignant mesenchymoma
adult rhabdomyosarcoma

nonmetastatic childhood soft tissue sarcoma
stage I adult soft tissue sarcoma
stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma
adult malignant mesenchymoma

Additional relevant MeSH terms:

Neoplasms, Muscle Tissue
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Irinotecan
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
Camptothecin
Pharmacologic Actions
Protein Synthesis Inhibitors
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Sarcoma

ClinicalTrials.gov processed this record on February 08, 2010