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.

Condition	Treatment or Intervention	Phase
adult soft tissue sarcoma	Drug: doxorubicin HCl liposome  Drug: ifosfamide  Procedure: chemotherapy	Phase I

Further Study Details: 

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.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

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

Denmark
      Aarhus University Hospital - Aarhus Sygehus - Norrebrogade, Aarhus,  DK-8000,  Denmark; Recruiting
Germany
      Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch, Berlin,  D-13122,  Germany; Recruiting

Study chairs or principal investigators

Ole Steen Nielsen, MD,  Aarhus University Hospital - Aarhus Sygehus - Norrebrogade   

Study ID Numbers:  CDR0000069197; EORTC-62002; NCT00030784
Record last reviewed:  August 2003
Last Updated:  December 6, 2004
Record first received:  February 14, 2002
ClinicalTrials.gov Identifier:  NCT00030784
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08