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

Alternate Title

Combination Chemotherapy and Dexrazoxane Followed by Surgery and Radiation Therapy in Treating Patients With Advanced Soft Tissue Sarcoma or Recurrent Bone Sarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 to 65	NCI	CHNMC-00050 00050, NCT00544778

Objectives

1. To evaluate the effectiveness of neoadjuvant dose-dense chemotherapy comprising doxorubicin hydrochloride, ifosfamide, and irinotecan hydrochloride in combination with dexrazoxane hydrochloride followed by surgery and radiotherapy in patients with advanced soft tissue sarcoma or recurrent bone sarcoma.
2. To evaluate the toxicities of this regimen in these patients.
3. To compare the duration of disease-free and overall survival of patients with advanced soft tissue sarcoma who receive this therapy on a neoadjuvant basis with historical controls.
4. To evaluate laboratory correlates of chemotherapy resistance for the cytotoxic agents used in this study.

Entry Criteria

Disease Characteristics:

• Diagnosis of 1 of the following:
  • Primary soft tissue sarcoma at high-risk* for recurrence, meeting any of the following criteria:
    • Previously untreated locally advanced, nonmetastatic disease
    • Advanced (metastatic) disease not amenable to standard or higher priority investigational neoadjuvant therapies
  • Recurrent bone sarcoma (e.g., osteogenic sarcoma, Ewing sarcoma, or peripheral neuroectodermal tumor)
    • Must have advanced locally recurrent or metastatic disease

   [Note: *High-risk is defined as high-grade, deep to fascia, and > 5 cm in greatest dimension]




• Measurable or nonmeasurable disease is not required



• Pre-chemotherapy consultation with surgery and radiation oncology is required for formulation of loco-regional therapy



• No gastrointestinal stromal cell sarcoma



• No alveolar soft part sarcoma



• No symptomatic brain metastases
  • No requirement for anticonvulsant or corticosteroid therapy

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy for recurrent (local or metastatic) soft tissue sarcoma
• Prior chemotherapy for recurrent bone sarcoma allowed provided the total dose of doxorubicin hydrochloride is ≤ 300 mg/m²
• No prior radiotherapy to > 25% of bone marrow
• At least 3 weeks since prior radiotherapy or chemotherapy

Patient Characteristics:

• Karnofsky performance status 70-100%
• Life expectancy ≥ 2 months
• Absolute neutrophil count ≥ 2,000/mm³
• Platelet count > 120,000/mm³
• Creatinine clearance > 50 mL/min
• Serum bilirubin ≤ 1.5 mg/dL
• SGOT or SGPT ≤ 2.5 times upper limit of normal
• Serum albumin ≥ 2.5 mg/dL
• LVEF ≥ 50% by MUGA scan
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No concurrent nonmalignant illness (e.g., cardiovascular, pulmonary, or CNS disease) that is poorly controlled with currently available treatment or is of such severity that the investigators deem it unwise for the patient to enter the study

Expected Enrollment

Outcomes

Response rate

Toxicity
Overall survival
Disease-free survival

Outline

Patients are stratified by type of sarcoma (soft tissue vs bone), prior treatment (untreated vs treated), and presence of metastases (yes vs no).

• Courses 1 and 2: Patients receive doxorubicin hydrochloride and dexrazoxane hydrochloride IV continuously over 96 hours. Treatment repeats every 3 weeks for 2 courses.



• Courses 3 and 4: Patients receive ifosfamide IV over 2 hours twice a day (every 12 hours) on days 1-3. Treatment repeats every 3 weeks for 2 courses.



• Courses 5 and 6: Patients receive irinotecan hydrochloride IV over 1 hour once a day on days 1-5 and 8-12. Treatment repeats every 3 weeks for 2 courses.

Patients also receive filgrastim (G-CSF) subcutaneously once a day beginning 3 days after completion of chemotherapy and continuing until blood counts recover.

Patients then undergo standard surgery and radiotherapy.

Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for MDR (multidrug resistance gene) protein expression via immunoperoxidase staining.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then once a year thereafter.

Trial Contact Information

Trial Lead Organizations

City of Hope Comprehensive Cancer Center

Warren Chow, MD, Protocol chair		Ph: 626-359-8111 ext. 62307; 800-826-4673 ext. 62307 Email: wchow@coh.org

Registry Information
Official Title		Phase II Trial of Neoadjuvant Dose-Dense Doxorubicin, Ifosfamide, and Irinotecan (CPT-11) for Advanced Soft Tissue and Recurrent Bone Sarcomas
Trial Start Date		2001-08-13
Registered in ClinicalTrials.gov		NCT00544778
Date Submitted to PDQ		2007-09-07
Information Last Verified		2007-10-04
NCI Grant/Contract Number		CA33572

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