Clinical trial NCT00227669: Gemcitabine With or Without Docetaxel as Second-Line Therapy in Treating Patients With Metastatic or Relapsed, Unresectable Uterine or Soft Tissue Leiomyosarcoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: 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
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2005-09-28
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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

Primary outcomes:
measure: Anti-tumoral activity (objective response rate)
timeFrame: 6 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 6 months
measure: Response duration
timeFrame: 3 years
measure: Tolerability
timeFrame: 3 years
measure: Dose intensity
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Biological markers
timeFrame: 3 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Angers
country: France
facility: Centre Paul Papin
city: Beauvais
country: France
facility: C.H.G. Beauvais
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: C.H.U. de Brest
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Hopital Edouard Herriot - Lyon
city: Marseille
country: France
facility: CHU de la Timone
city: Marseille
country: France
facility: CHU Nord
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Nantes
country: France
facility: CHR Hotel Dieu
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Institut Curie Hopital
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Hopital Cochin
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Priest en Jarez
country: France
facility: Institut de Cancerologie de la Loire
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: CHU de la Timone
name: Florence Duffaud, MD
role: STUDY_CHAIR
References:
citation: 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.