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

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Drug: docetaxel; Drug: gemcitabine hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • Centre Hospitalier Universitaire d'Amiens
  • Angers, France, 49036
    • Centre Paul Papin
  • Beauvais, France, 60021
    • C.H.G. Beauvais
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Brest, France, 29609
    • C.H.U. de Brest
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Colmar, France, 68024
    • Hôpital Louis Pasteur
  • Dijon, France, 21079
    • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69437
    • Hopital Edouard Herriot - Lyon
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13385
    • CHU de la Timone
  • Marseille, France, 13915
    • CHU Nord
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nantes, France, 44093
    • CHR Hotel Dieu
  • Nantes-Saint Herblain, France, 44805
    • Centre Regional Rene Gauducheau
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Orleans, France, 45067
    • CHR D'Orleans - Hopital de la Source
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Paris, France, 75674
    • Hopital Cochin
  • Paris, France, 75475
    • Hopital Saint-Louis
  • Paris, France, 75248
    • Institut Curie Hopital
  • Poitiers, France, 86021
    • CHU Poitiers
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Saint Cloud, France, 92211
    • Centre René Huguenin
  • Saint Priest en Jarez, France, 42270
    • Institut de Cancerologie de La Loire
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Tours, France, 37044
    • Centre Hospitalier Universitaire Bretonneau de Tours
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I: Gemcitabine; 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
Experimental: Arm II: Gemcitabine + Docetaxel; 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; Drug: gemcitabine hydrochloride

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Study Chair: Florence Duffaud, MD, CHU de la Timone

Publications and helpful links

General Publications

• Duffaud F, Bui BN, Penel N, et al.: A FNCLCC French Sarcoma Group--GETO multicenter randomized phase II study of gemcitabine (G) versus gemcitabine and docetaxel (G+D) in patients with metastatic or relapsed leiomyosarcoma (LMS). [Abstract] J Clin Oncol 26 (Suppl 15): A-10511, 2008.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 26, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: adult leiomyosarcoma; stage IV adult soft tissue sarcoma; recurrent adult soft tissue sarcoma; stage IV uterine sarcoma; recurrent uterine sarcoma; uterine leiomyosarcoma; stage III uterine sarcoma; stage III adult soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Sarcoma; Leiomyosarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gemcitabine; Docetaxel
• Other Study ID Numbers: CDR0000443572; FRE-FNCLCC-SARCOME-07/0410; EU-20518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared at an individual level.