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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether giving gemcitabine together with docetaxel is more effective than giving gemcitabine alone as second-line therapy in treating uterine or soft tissue leiomyosarcoma. PURPOSE: This randomized phase II trial is studying gemcitabine and docetaxel to see how well they work compared to gemcitabine alone as second-line therapy in treating patients with metastatic or relapsed, unresectable uterine or soft tissue leiomyosarcoma.

Detailed Description
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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.

Official Title
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Randomized Phase II Study Evaluating the Efficacy of Gemcitabine Versus the Gemcitabine/Docetaxel Combination as Second Line Treatment in Metastatic or Relapsed and Inoperable Uterine or Soft Tissue Leiomyosarcomas

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: docetaxel
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I: Gemcitabine<br>Gemcitabine at Day 1, Day 8 and Day 15. No treatment at Day 22. 1 cycle = 28 days. Treatment duration: 8 months | Drug: gemcitabine hydrochloride<br> <br> |
| Experimental: Arm II: Gemcitabine + Docetaxel<br>Gemcitabine at Day 1 and Day 8. No treatment at Day 15. Docetaxel at Day 8. 1 cycle = 21 days. Treatment duration: 6 months | Drug: docetaxel<br> <br> Drug: gemcitabine hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumoral activity (objective response rate) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 6 months | 
| Response duration |  | 3 years | 
| Tolerability |  | 3 years | 
| Dose intensity |  | 3 years | 
| Overall survival |  | 3 years | 
| Biological markers |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uterine leiomyosarcoma, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma, recurrent adult soft tissue sarcoma, stage III uterine sarcoma, stage IV uterine sarcoma, recurrent uterine sarcoma, adult leiomyosarcoma