Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving irinotecan together with carboplatin as upfront window therapy (first-line therapy) works in treating patients with newly diagnosed intermediate-risk or high-risk rhabdomyosarcoma.

Further Study Information

OBJECTIVES:

Primary

• Determine the response rate in patients with newly diagnosed intermediate- or high-risk rhabdomyosarcoma treated with upfront window therapy comprising irinotecan and carboplatin.

• Determine the acute toxic effects of this regimen combined with radiotherapy in these patients.

• Determine the safety and feasibility of this regimen in these patients.

• Determine the rate of local control achieved in patients treated with this regimen in combination with intensity-modulated radiotherapy.

• Determine the safety and feasibility of administering maintenance therapy comprising irinotecan to patients with high-risk rhabdomyosarcoma treated with this regimen.

Secondary

• Correlate, preliminarily, in vitro measurements of angiogenesis with clinical features (extent of disease), response to therapy, and outcome in patients treated with this regimen.

• Determine, preliminarily, the efficacy of this regimen, in terms of improved outcomes, in these patients.

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.

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

Eligibility 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

PATIENT CHARACTERISTICS:

Age

• 30 and under at diagnosis

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3*

• Hemoglobin ≥ 9 g/dL*

• Platelet count ≥ 100,000/mm^3* 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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Memorial Sloan-Kettering Cancer Center

Leonard H. Wexler

Study Chair

U.S.A.
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Leonard H. Wexler	Ph: 212-639-7990
			Email: wexlerl@mskcc.org

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00077285
Information obtained from ClinicalTrials.gov on February 06, 2012

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