Liposomal Doxorubicin Plus Ifosfamide in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining liposomal doxorubicin with ifosfamide in treating patients who have advanced or metastatic soft tissue sarcoma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of ifosfamide in combination with doxorubicin HCl liposome in patients with previously untreated advanced or metastatic soft tissue sarcoma. Determine the objective response in patients treated with this regimen. Determine the dose-limiting toxicity in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of ifosfamide. Patients receive doxorubicin HCl liposome IV over 1 hour on day 1 and ifosfamide IV over 4 hours on days 1-3 OR on days 1-4 (for patients enrolled on dose level 6). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ifosfamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study.

Official Title
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Phase I Study To Determine The Safety Of Caelyx (Doxorubin HCI, Pegylated Liposomal) In Combination With Ifosfamide In Previously Untreated Adult Patients With Advanced And/Or Metastatic Soft Tissues Sarcomas

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: ifosfamide
* Drug: pegylated liposomal doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed soft tissue sarcoma Advanced and/or metastatic disease Must be of any of the following types: Malignant fibrous histiocytoma Liposarcoma (excluding lipomas and well-differentiated liposarcomas) Rhabdomyosarcoma Synovial sarcoma Malignant paraganglioma Fibrosarcoma Leiomyosarcoma Angiosarcoma Neurogenic sarcoma Sarcoma not otherwise specified Paraffin blocks and slides must be available Measurable disease Osseous lesions and pleural effusions are not considered measurable disease Evidence of progressive disease within the past 6 weeks The following conditions are excluded: Gastrointestinal stromal tumors Malignant mesothelioma Chondrosarcoma Neuroblastoma Osteosarcoma Ewing's sarcoma Embryonal rhabdomyosarcoma No symptomatic or known CNS metastases PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: WHO 0-1 Life expectancy: Not specified Hematopoietic: WBC at least 4,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.75 mg/dL Albumin at least 2.5 g/dL Renal: Creatinine no greater than 1.4 mg/dL Creatinine clearance at least 65 mL/min Cardiovascular: Ejection fraction at least 50% by echocardiogram or isotopic methods No history of cardiovascular disease Other: No other prior or concurrent primary malignancies except adequately treated carcinoma in situ of the cervix or basal cell carcinoma No other severe medical illness No psychosis No psychological, familial, sociological, or geographical condition that would preclude study participation Not pregnant Fertile patients must use effective contraception (barrier method for men) during and for 6 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for advanced disease No other concurrent systemic chemotherapy for malignancy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to sole indicator lesion Concurrent radiotherapy allowed except to sole indicator lesion Surgery: Not specified Other: No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ifosfamide|nan|
|Drug: pegylated liposomal doxorubicin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult angiosarcoma, adult fibrosarcoma, adult leiomyosarcoma, adult liposarcoma, adult neurofibrosarcoma, adult synovial sarcoma, stage III adult soft tissue sarcoma, adult alveolar soft-part sarcoma, adult epithelioid sarcoma, adult malignant fibrous histiocytoma, adult malignant hemangiopericytoma, adult malignant mesenchymoma, adult rhabdomyosarcoma, stage IV adult soft tissue sarcoma