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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

November 1, 1999
February 12, 2014
September 1999
January 2005   (final data collection date for primary outcome measure)
Event Free Survival [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00003955 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Metastatic Rhabdomyosarcoma or Sarcoma
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

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.

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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
Sarcoma
  • Biological: dactinomycin
  • Biological: filgrastim
  • Biological: pegfilgrastim
  • Biological: sargramostim
  • Drug: cyclophosphamide
  • Drug: irinotecan hydrochloride
  • Drug: vincristine sulfate
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
77
October 2009
January 2005   (final data collection date for primary outcome measure)

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
Both
up to 49 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Netherlands,   New Zealand,   Puerto Rico,   Switzerland
 
NCT00003955
D9802, COG-D9802, IRS-D9802, CCG-D9802, POG-D9802, CDR0000067154
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Alberto S. Pappo, MD Texas Children's Cancer Center
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP