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

Unicancer

Status and phase: Completed; Phase 2

Conditions: Sarcoma

Treatments: Drug: gemcitabine hydrochloride; Drug: docetaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT00227669

CDR0000443572

FRE-FNCLCC-SARCOME-07/0410

EU-20518

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Arm I: Gemcitabine

Active Comparator group

Description:

Gemcitabine at Day 1, Day 8 and Day 15. No treatment at Day 22. 1 cycle = 28 days. Treatment duration: 8 months

Treatment:

Drug: gemcitabine hydrochloride

Arm II: Gemcitabine + Docetaxel

Experimental group

Description:

Gemcitabine at Day 1 and Day 8. No treatment at Day 15. Docetaxel at Day 8. 1 cycle = 21 days. Treatment duration: 6 months

Treatment:

Drug: gemcitabine hydrochloride

Drug: docetaxel