Clinical trial NCT01442662: Efficacy of Gemcitabine With Pazopanib as Second Line Treatment in Patient With Metastatic or Relapsed Uterine
Official title: Phase II Multicenter Study to Determine the Efficacy of Gemcitabine With Pazopanib as Second Line Treatment in Patients With Metastatic or Relapsed Uterine or Soft Tissue Leiomyosarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leiomyosarcoma
Keywords: Metastatic or relapsed uterine or soft tissue leiomyosarcoma
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2011-09-28
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this research is to study the activity of pazopanib in second line after anthracyclines in extra uterus and uterine LMS in association with gemcitabine.

Detailed description: Primary Objectives:

To determine the PFS using combination of gemcitabine and pazopanib in patients with metastasis or relapse leiomyosarcoma (uterine or soft tissue)who have already received s first line anthracycline based therapy.

Secondary objectives:

To determine the disease control rate To determine the response rate To determine toxicities associated with combined gemcitabine and pazopanib To determine correlation between metabolic response and PFS

Design:

All eligible patients entering the study will receive daily oral pazopanib at 800mg, supplied as 200 mg aqueous film-coated tablets and 2 intravenous gemcitabine every three weeks (8 cycles max).

The treatment will continue until the development of unacceptable toxicity or evidence of disease progression or until patient's / investigator's decision of withdrawal.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of metastatic or relapsed of uterine or soft tissue leiomyosarcoma previously treated with one line of chemotherapy with at least an anthracycline. Patients who have received adjuvant therapy less than one year before relapse were considered to have received a first line therapy for metastatic disease)
* Delay between the end of previous treatment (chemotherapy, hormonotherapy, radiotherapy, immunotherapy, surgery or tumor embolisation) must be \> 4 weeks
* At least one measurable lesion with RECIST criteria with progressive disease between the last 6 weeks between inclusion. One target at least must be in a non irradiated area
* performance status ECOG ≤ 2
* Age ≥ 18 years
* Subjects must provide written informed consent prior to performance of study-specific procedures, and must be willing to comply with treatment and follow up
* Adequate hematologic function
* Adequate coagulation function
* Adequate renal function
* Adequate liver function
* Patients must be affiliated to a Social Health Insurance
* Women of childbearing potential must be using a medically accepted method of contraception and must have a negative serum pregnancy test within 14 days of enrollment and/or urine pregnancy test 72 hours prior to the administration of the first study treatment.
* LVEF ≥ site limits

Main Exclusion Criteria:

* Other uterine or soft tissue sarcomas
* Symptomatic or known brain metastasis
* Radiation therapy on the only evaluable lesion
* Anti coagulant treatment
* strong inhibitors or inducers of the isoenzyme CYP3A4 treatment
* Known sero-positivity (HIV, HbC, HbS)or uncontrolled infection
* other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* Clinically significant gastrointestinal abnormalities that may affect the absorption of the IP
* Corrected QT interval \> 480 msec
* Other serious underlying pathology that would preclude study treatment
* Calcium and magnesium levels inferior to standard levels (measured within 14 days before the first pazopanib dose) and potassium levels inferior to standard levels (measured within 72 hours before the first pazopanib dose)

Primary outcomes:
measure: Progression Free Survival
timeFrame: 9 months
Secondary outcomes:
measure: disease control rate and overall response rate
timeFrame: 12 weeks
measure: Safety of the combination Gemcitabine-Pazopanib
timeFrame: during the entire trial
measure: metabolic response by using PET scan
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre G.F Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: CHU Timone
city: Montpellier
country: France
facility: Centre Val d'Aurelle Paul Lamarque
city: Nantes Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest/Centre René Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie - Hôpital Claudius Regaud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Institut Curie - Hopital René Huguenin
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre les Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Patricia Pautier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pautier P, Penel N, Ray-Coquard I, Italiano A, Bompas E, Delcambre C, Bay JO, Bertucci F, Delaye J, Chevreau C, Cupissol D, Bozec L, Eymard JC, Saada E, Isambert N, Guillemet C, Rios M, Piperno-Neumann S, Chenuc G, Duffaud F. A phase II of gemcitabine combined with pazopanib followed by pazopanib maintenance, as second-line treatment in patients with advanced leiomyosarcomas: A unicancer French Sarcoma Group study (LMS03 study). Eur J Cancer. 2020 Jan;125:31-37. doi: 10.1016/j.ejca.2019.10.028. Epub 2019 Dec 10.