Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Metastatic Rhabdomyosarcoma or Sarcoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00003955
First received: November 1, 1999
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy use 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 more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy combined with radiation therapy in treating patients who have metastatic rhabdomyosarcoma or sarcoma.


Condition Intervention Phase
Sarcoma
Biological: dactinomycin
Biological: filgrastim
Biological: pegfilgrastim
Biological: sargramostim
Drug: cyclophosphamide
Drug: irinotecan hydrochloride
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II "Up-Front Window Study" of Irinotecan (CPT-11) Followed by Multimodal, Multiagent, Therapy for Selected Children and Adolescents With Newly Diagnosed Stage 4/Clinical Group IV Rhabdomyosarcoma: An IRS-V Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event Free Survival [ Designated as safety issue: No ]

Enrollment: 77
Study Start Date: September 1999
Study Completion Date: October 2009
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the response rate of patients with newly diagnosed high-risk metastatic stage IV/clinical group IV rhabdomyosarcoma treated with upfront window therapy comprising irinotecan and vincristine.
  • Determine the toxic effects of this regimen in these patients.
  • Determine the toxic effects of this regimen when given in alternating courses with vincristine, dactinomycin, and cyclophosphamide (VAC) as continuation therapy in patients with partial or complete response.
  • Determine the overall and failure-free survival of patients treated with irinotecan and vincristine followed by VAC alone or VAC alternating with vincristine and irinotecan plus radiotherapy.
  • Determine the pharmacokinetics of irinotecan and vincristine in these patients.

OUTLINE:

  • Upfront window therapy: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 60 minutes on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2 courses. Patients experiencing partial or complete response proceed to regimen A. Patients experiencing stable or progressive disease proceed to regimen B.

    • Regimen A: Patients receive vincristine IV over 1 minute weekly on weeks 6-13, 15-19, 23-27, 29, 32-35, 38-39, and 41; dactinomycin IV over 1 minute weekly on weeks 6, 12, 23, 29, 35, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 12, 16, 19, 23, 29, 35, and 41. Patients also receive irinotecan IV over 1 hour daily, 5 days a week, on weeks 9, 10, 26, 27, 32, 33, 38, and 39 and undergo radiotherapy daily, 5 days a week, on weeks 15-22.
    • Regimen B: Patients receive vincristine as in regimen A; dactinomycin IV over 1 minute weekly on weeks 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41 and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients receive radiotherapy as in regimen A.

Patients who do not receive upfront window irinotecan/vincristine therapy are treated with standard therapy.

  • Standard therapy: Patients receive vincristine IV over 1 minute weekly on weeks 0-13, 15-19, 23-27, 29, 32-35, 38, and 41; dactinomycin IV over 1 minute weekly on weeks 0, 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 0, 3, 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients without evidence of intracranial extension receive radiotherapy once daily, 5 days a week, during weeks 15-22. Patients with evidence of intracranial extension, or who require emergency radiotherapy, receive radiotherapy during weeks 0-6. Dactinomycin is withheld during radiotherapy.

All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) beginning 24 hours after completion of each course of chemotherapy and continuing until blood counts recover. Alternatively, patients may receive pegfilgrastim SC beginning 24-36 hours after completion of each course of chemotherapy and continuing until blood counts recover.

Patients are followed every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 9-24 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic stage IV/clinical group IV rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma

    • No metastatic embryonal tumors in patients under 10 years of age, regardless of primary site
    • Metastatic tumors of parameningeal sites eligible
  • Bidimensionally measurable disease
  • No positive cerebrospinal fluid cytology or multiple intracranial metastases
  • Patients presenting with the following are only eligible for continuation therapy and may not receive irinotecan/vincristine upfront window therapy:

    • Evidence of base of skull erosion or skull metastatic disease that displaces or indents the dura, compresses the brain parenchyma, or causes evidence of cranial nerve palsy
    • Tumor that touches or displaces the spinal cord
    • Evidence of intracranial primary tumor extension
    • Tumors that could cause potentially life-threatening complications (e.g., renal, airway) with progression due to location and/or growth rate
    • Requires emergency radiotherapy
    • Lab values are consistent with disseminated intravascular coagulation

PATIENT CHARACTERISTICS:

Age:

  • Under 50 (alveolar rhabdomyosarcoma, undifferentiated sarcoma, and ectomesenchymoma patients)
  • 10 to 49 (embryonal histology patients)

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • Absolute neutrophil count greater than 1,000/mm^3*
  • Platelet count greater than 150,000/mm^3* NOTE: *Unless there is tumor involvement of bone marrow

Hepatic:

  • Bilirubin less than 1.5 mg/dL
  • PT, PTT, and fibrinogen less than 1.5 times upper limit of normal

Renal:

  • Creatinine less than 1.2 mg/dL

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Prior steroids allowed

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy

Surgery:

  • No more than 42 days since prior initial surgical procedure, including biopsy for diagnosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003955

  Show 237 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Alberto S. Pappo, MD Texas Children's Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003955     History of Changes
Other Study ID Numbers: D9802, COG-D9802, IRS-D9802, CCG-D9802, POG-D9802, CDR0000067154
Study First Received: November 1, 1999
Last Updated: February 12, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
embryonal childhood rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
childhood malignant mesenchymoma
previously untreated childhood rhabdomyosarcoma
adult rhabdomyosarcoma
adult malignant mesenchymoma
stage IV adult soft tissue sarcoma

Additional relevant MeSH terms:
Rhabdomyosarcoma
Sarcoma
Myosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Cyclophosphamide
Dactinomycin
Irinotecan
Vincristine
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protein Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014