Efficacy of Gemcitabine With Pazopanib as Second Line Treatment in Patient With Metastatic or Relapsed Uterine

Phase 2

Completed

• Conditions: Leiomyosarcoma
• Interventions: Drug: pazopanib + gemcitabine

• Registration Number: NCT01442662
• Lead Sponsor: UNICANCER

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.

Study Timeline

• Study First Submitted: 2011-08-10
• Study Start: 2011-09
• Study First Submitted QC: 2011-09-27
• Study First Posted: 2011-09-28
• Primary Completion: 2018-03
• Study Completion: 2019-05-28
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-29
• Last Update Posted: 2020-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 106

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
pazopanib, gemcitabine	pazopanib + gemcitabine	pazopanib tablets (200mg) per os, 800mg/day continuously gemcitabine IV, 2 injection per cycle

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	9 months	To assess the 9-month Progression Free Survival in Patients With Metastatic or Relapsed Uterine or Soft Tissue Leiomyosarcomas and treated with Gemcitabine and Pazopanib

Secondary Outcome Measures

Name	Time	Method
disease control rate and overall response rate	12 weeks
Safety of the combination Gemcitabine-Pazopanib	during the entire trial	The severity of the adverse events and toxicity will be graded according to the NCI CTC-AE v4.0
metabolic response by using PET scan	6 weeks	First PET scan at baseline and the second one at 6 weeks after the first administration

Trial Locations

Locations (17)

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Centre François Baclesse; 🇫🇷 Caen, France

Institut Curie - Hopital René Huguenin; 🇫🇷 Saint Cloud, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Institut Bergonié; 🇫🇷 Bordeaux, France

Centre Jean Perrin; 🇫🇷 Clermont Ferrand, France

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut de Cancérologie de l'Ouest/Centre René Gauducheau; 🇫🇷 Nantes Saint Herblain, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

CHU Timone; 🇫🇷 Marseille, France

Centre G.F Leclerc; 🇫🇷 Dijon, France

Centre Val d'Aurelle Paul Lamarque; 🇫🇷 Montpellier, France

Institut Curie - Hôpital Claudius Regaud; 🇫🇷 Paris, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France

Centre Alexis Vautrin; 🇫🇷 Vandoeuvre les Nancy, France