Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

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

Summary: 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: 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.

Eligibility: 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

Relevance to patient case: not relevant