Efficacy of Gemcitabine With Pazopanib as Second Line Treatment in Patient With Metastatic or Relapsed Uterine (LMS03)

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

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.

Study Overview

• Status: Completed
• Conditions: Leiomyosarcoma
• Intervention / Treatment: Drug: pazopanib + 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 Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin
  • Dijon, France, 21034
    • Centre G.F Leclerc
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Marseille, France, 13385
    • CHU Timone
  • Montpellier, France, 34298
    • Centre Val d'Aurelle Paul Lamarque
  • Nantes Saint Herblain, France, 44806
    • Institut de Cancérologie de l'Ouest/Centre René Gauducheau
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75005
    • Institut Curie - Hopital Claudius Régaud
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint Cloud, France, 92210
    • Institut Curie - Hôpital René Huguenin
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Vandoeuvre les Nancy, France, 54511
    • Centre Alexis Vautrin
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pazopanib, gemcitabine; pazopanib tablets (200mg) per os, 800mg/day continuously gemcitabine IV, 2 injection per cycle	Drug: pazopanib + gemcitabine; pazopanib tablets (200mg) per os, 800mg/day continuously gemcitabine IV, 2 injection per cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	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	9 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Principal Investigator: Patricia Pautier, MD, Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): May 28, 2019

Study Registration Dates

• First Submitted: August 10, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Metastatic or relapsed uterine or soft tissue leiomyosarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Muscle Tissue; 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; Gemcitabine
• Other Study ID Numbers: SARCOME 11/1101; 2011-001308-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: PD will not be shared at an individual level, they will be part of the study database including all enrolled patients