Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Under 50	NCI	COG-D9802 IRS-D9802, CCG-D9802, POG-D9802, NCT00003955

Objectives

1. 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.
2. Determine the toxic effects of this regimen in these patients.
3. 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.
4. 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.
5. Determine the pharmacokinetics of irinotecan and vincristine in these patients.

Entry 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

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

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/mm³*
• Platelet count greater than 150,000/mm³*

 [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

Expected Enrollment

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

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.

Pappo AS, Lyden E, Breitfeld P, et al.: Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. J Clin Oncol 25 (4): 362-9, 2007.[PUBMED Abstract]

Lager JJ, Lyden ER, Anderson JR, et al.: Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 24 (21): 3415-22, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Alberto Pappo, MD, Protocol chair		Ph: 832-822-4200

Registry Information
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
Trial Start Date		2001-03-27
Registered in ClinicalTrials.gov		NCT00003955
Date Submitted to PDQ		1999-06-24
Information Last Verified		2004-10-18
NCI Grant/Contract Number		U10-CA24507

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