Troglitazone in Treating Patients With Liposarcoma

RATIONALE: Troglitazone may help liposarcoma cells develop into normal cells.

PURPOSE: Phase II trial to study the effectiveness of troglitazone in treating patients with malignant liposarcoma.

OBJECTIVES: I. Evaluate the clinical activity of troglitazone in patients with malignant liposarcoma. II. Evaluate the tolerance and safety of troglitazone in this patient population.

OUTLINE: This is an open label trial. All patients are given a single dose of oral troglitazone daily. Patients continue to receive troglitazone as long as their disease responds to treatment or remains stable.

PROJECTED ACCRUAL: Initially, 14 patients of each of the 5 subtypes of liposarcoma will be accrued. If 1 or more patients show evidence of biological response, an additional 16 patients of each subtype will be accrued for a total of 30 per subtype.

• Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6.
• Demetri GD, Spiegelman B, Fletcher CD, et al.: Differentiation of liposarcomas in patients treated with the PPAR g ligand troglitazone: documentation of biologic activity in myxoid/round cell and pleomorphic subtypes. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A2064, 535a, 1999.

DISEASE CHARACTERISTICS: Histologically proven liposarcoma that is incurable by standard surgery Measurable or evaluable disease required No active CNS involvement or leptomeningeal disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT less than 5 times upper normal limit Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No poorly controlled atrial arrhythmias, angina pectoris, or myocardial infarction within past 6 months No symptomatic congestive heart failure, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft within past 3 months Other: Not pregnant or nursing Fertile patients must use effective contraception No known active retroviral disease

PRIOR CONCURRENT THERAPY: Recovered from toxic effects of all prior therapy No concurrent cytotoxic therapy Biologic therapy: Not specified Chemotherapy: Prior chemotherapy allowed Endocrine therapy: No concurrent hormonal therapy Radiotherapy: Prior radiation therapy for metastatic disease allowed No radiotherapy to sole site of measurable disease within past 6 months Surgery: Not specified