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

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00077285

Purpose

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.

Condition	Intervention	Phase
Sarcoma	Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: irinotecan hydrochloride Drug: vincristine sulfate Procedure: conventional surgery Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response rate [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Safety and feasibility [ Designated as safety issue: Yes ]
Rate of local control [ Designated as safety issue: No ]

Secondary Outcome Measures:

Correlation of in vitro measurements of angiogenesis with clinical features (extent of disease), response to therapy, and outcome [ Designated as safety issue: No ]
Efficacy in terms of improved outcomes [ Designated as safety issue: No ]

Estimated Enrollment:	61
Study Start Date:	October 2003
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

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Detailed Description:

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

Ages Eligible for Study:	up to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00077285

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Leonard H. Wexler, MD 212-639-7990 wexlerl@mskcc.org

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Leonard H. Wexler, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Leonard H. Wexler )
Study ID Numbers:	CDR0000350083, MSKCC-03099
Study First Received:	February 10, 2004
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00077285 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

previously untreated childhood rhabdomyosarcoma
embryonal childhood rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
adult rhabdomyosarcoma
stage IV adult soft tissue sarcoma
metastatic childhood soft tissue sarcoma

nonmetastatic childhood soft tissue sarcoma
childhood malignant mesenchymoma
adult malignant mesenchymoma
stage III adult soft tissue sarcoma
stage II adult soft tissue sarcoma
stage I adult soft tissue sarcoma

Additional relevant MeSH terms:

Neoplasms, Muscle Tissue
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Irinotecan
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Razoxane
Neoplasms, Connective and Soft Tissue
Therapeutic Uses
Etoposide
Alkylating Agents
Rhabdomyosarcoma
Neoplasms by Histologic Type

Myosarcoma
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Cardiovascular Agents
Carboplatin
Immunosuppressive Agents
Doxorubicin
Camptothecin
Pharmacologic Actions
Ifosfamide
Neoplasms
Tubulin Modulators
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 25, 2009