Gemcitabine With or Without Docetaxel as Second-Line Therapy in Treating Patients With Metastatic or Relapsed, Unresectable Uterine or Soft Tissue Leiomyosarcoma

OBJECTIVES:

Primary

• Compare the anti-tumor activity, in terms of objective response rate, in patients with metastatic or relapsed, unresectable uterine or soft tissue leiomyosarcoma treated with gemcitabine with vs without docetaxel as second-line therapy.

Secondary

• Compare the progression-free survival of patients treated with these regimens.
• Compare the response duration and overall survival of patients treated with these regimens.
• Compare the tolerability and dose intensity of these regimens in these patients.
• Determine biological markers with a predictive value for response to these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to location of leiomyosarcoma (uterine vs soft tissue). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine on days 1, 8, and 15. Treatment repeats every 4 weeks for 2-8 courses.
• Arm II: Patients receive gemcitabine on days 1 and 8 and docetaxel on day 8. Treatment repeats every 3 weeks for 2-8 courses.

PROJECTED ACCRUAL: A minimum of 80 patients (40 per stratum and treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed uterine or soft tissue leiomyosarcoma, meeting ≥ 1 of the following criteria:

• Metastatic disease
• Relapsed and unresectable disease
• Prior treatment with a first-line anthracycline-based chemotherapy regimen required

• Relapsed disease > 1 year after adjuvant chemotherapy is considered untreated disease
• If relapsed disease occurs < 1 year after adjuvant therapy, then adjuvant therapy is considered a first-line treatment
• At least 1 measurable lesion, defined as the following:

• At least 1 target lesion must be located in a non-irradiated area
• Obvious disease progression within the past 6 weeks
• No other uterine sarcomas, including any of the following:

• Carcinosarcoma
• Endometrial stroma sarcoma
• Other soft tissue sarcoma
• No symptomatic or known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• No specific hepatic contraindication to study treatment
• Hepatitis B core and hepatitis B surface antigen negative

Renal

• Creatinine < 1.5 times ULN
• No specific renal contraindication to study treatment

Cardiovascular

• No specific cardiac contraindication to study treatment

Immunologic

• HIV negative
• No specific allergic contraindication to study treatment
• No active infection

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other serious underlying pathology that would preclude study treatment
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No neurotoxicity > grade 2
• No psychological, sociological, or geographical condition that would preclude study compliance or follow-up schedule
• No prior or concurrent psychiatric illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy
• No prior allogeneic graft or autologous graft

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy
• No prior gemcitabine and/or taxane (i.e., docetaxel or paclitaxel)

Endocrine therapy

• More than 4 weeks since prior hormonal therapy

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to the only evaluable lesion

Surgery

• Not specified

Other

• No concurrent participation in another clinical trial using an experimental agent