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

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.

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.

• Drug: ifosfamide
• Drug: pegylated liposomal doxorubicin hydrochloride

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