Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Irinotecan and Carboplatin as Upfront Window Therapy in Treating Patients With Newly Diagnosed Intermediate-Risk or High-Risk Rhabdomyosarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	30 and under at diagnosis	NCI	MSKCC-03099 NCT00077285

Objectives

Primary

1. Determine the response rate in patients with newly diagnosed intermediate- or high-risk rhabdomyosarcoma treated with upfront window therapy comprising irinotecan and carboplatin.
2. Determine the acute toxic effects of this regimen combined with radiotherapy in these patients.
3. Determine the safety and feasibility of this regimen in these patients.
4. Determine the rate of local control achieved in patients treated with this regimen in combination with intensity-modulated radiotherapy.
5. Determine the safety and feasibility of administering maintenance therapy comprising irinotecan to patients with high-risk rhabdomyosarcoma treated with this regimen.

Secondary

1. Correlate, preliminarily, in vitro measurements of angiogenesis with clinical features (extent of disease), response to therapy, and outcome in patients treated with this regimen.
2. Determine, preliminarily, the efficacy of this regimen, in terms of improved outcomes, in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed rhabdomyosarcoma (RMS), undifferentiated sarcoma, or ectomesenchymoma, meeting criteria for 1 of the following:
  • High-risk disease
    • Distant metastases (stage 4, group IV)
  • Intermediate-risk disease
    • Nonmetastatic undifferentiated sarcoma OR alveolar RMS OR ectomesenchymoma with alveolar features (regardless of age, site, size, stage, or degree of initial surgical resection)
    • Stage 2 or 3, group III embryonal RMS OR ectomesenchymoma with embryonal features



• Newly diagnosed
  • Previously untreated



• Biopsy or definitive surgery required within the past 42 days

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior steroids allowed

Radiotherapy

• No prior radiotherapy, except limited, emergent radiotherapy (e.g., treatment of threatened airway or spinal cord compromise)

Surgery

• See Disease Characteristics

Patient Characteristics:

Age

• 30 and under at diagnosis

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³*
• Hemoglobin ≥ 9 g/dL*
• Platelet count ≥ 100,000/mm³*

 [Note: *Unless there is bone marrow infiltration by tumor or presence of disseminated intravascular coagulation]

Hepatic

• Bilirubin < 2.5 times upper limit of normal (ULN)*
• SGOT and SGPT < 2.5 times ULN*

 [Note: *Unless there is hepatic involvement by tumor]

Renal

• Creatinine normal for age

  OR

• Creatinine clearance or nuclear glomerular filtration rate at least 80 mL/min (in the absence of obstructive hydronephrosis)

Cardiovascular

• Shortening fraction ≥ 28% by echocardiogram

  OR

• LVEF ≥ 50% by MUGA

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 24-61 patients will be accrued for this study within 3 years.

Outcomes

Response rate
Toxicity
Safety and feasibility
Rate of local control

Correlation of in vitro measurements of angiogenesis with clinical features (extent of disease), response to therapy, and outcome
Efficacy in terms of improved outcomes

Outline

This is a pilot study.

• Courses 1 and 2: Patients receive carboplatin IV over 1 hour on day 1 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2 courses.



• Courses 3-5: Patients receive vincristine IV on days 1, 8, and 15; dexrazoxane IV over 15-30 minutes, doxorubicin IV over 15-30 minutes, and cyclophosphamide IV over 1 hour on days 1 and 2; and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on approximately day 3 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 3 courses.

  Some patients may undergo surgical resection of the tumor after completion of course 5. After course 5, patients undergo radiotherapy once daily, 5 days a week, for 4-5.5 weeks.




• Courses 6 and 7*: Patients receive vincristine IV and carboplatin IV over 1 hour on day 1; irinotecan IV over 1 hour on days 1-5 and 8-12; and G-CSF SC once daily beginning on approximately day 13 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses.

   [Note: *Patients who develop disease progression during courses 1 or 2 do not receive further irinotecan and carboplatin. Instead, patients receive ifosfamide and etoposide as in courses 8 and 9.]




• Courses 8 and 9: Patients receive vincristine IV on day 1; etoposide IV over 1 hour and ifosfamide IV over 2 hours on days 1-5; and G-CSF SC once daily beginning on approximately day 6 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses.



• Course 10: Patients receive vincristine IV on days 1, 8, 15, 22, 29, 36, and 43; dexrazoxane IV over 15-30 minutes, doxorubicin IV over 15-30 minutes, and cyclophosphamide IV over 1 hour on days 1 and 2; and filgrastim SC beginning on approximately day 3 and continuing until blood counts recover (1 course).



• Course 11 and 12: Patients receive etoposide IV over 1 hour and ifosfamide IV over 2 hours on days 1-5 and G-CSF SC once daily beginning on approximately day 6 and continuing until blood counts recover. Treatment repeats every 21 days for a total of 2 courses.

  Patients with high-risk disease proceed to maintenance therapy.




• Maintenance therapy*: Patients receive irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 6 courses.

   [Note: *Patients who develop disease progression during courses 1 or 2 do not receive further irinotecan.]

In all courses, treatment continues in the absence of unacceptable toxicity or disease progression or recurrence after initial response.

Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Leonard Wexler, MD, Protocol chair		Ph: 212-639-7990; 800-525-2225 Email: wexlerl@mskcc.org

U.S.A.
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Leonard Wexler, MD	Ph:  212-639-7990 800-525-2225
			Email: wexlerl@mskcc.org
		Paul Meyers, MD	Ph:  212-639-5952 800-525-2225
			Email: meyersp@mskcc.org

Registry Information
Official Title		A Pilot Phase II Trial Of Irinotecan Plus Carboplatin, And Irinotecan Maintenance Therapy (High-Risk Patients Only), Integrated Into The Upfront Therapy Of Newly Diagnosed Patients With Intermediate - And High-Risk Rhabdomyosarcoma
Trial Start Date		2003-10-28
Trial Completion Date		2010-10-28 (estimated)
Registered in ClinicalTrials.gov		NCT00077285
Date Submitted to PDQ		2003-12-16
Information Last Verified		2009-07-05
NCI Grant/Contract Number		P30-CA08748

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