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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Leiomyosarcoma

Intervention / Treatment
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* Drug: pazopanib + gemcitabine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pazopanib, gemcitabine<br>pazopanib tablets (200mg) per os, 800mg/day continuously gemcitabine IV, 2 injection per cycle | Drug: pazopanib + gemcitabine<br>* pazopanib tablets (200mg) per os, 800mg/day continuously gemcitabine IV, 2 injection per cycle<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic or relapsed uterine or soft tissue leiomyosarcoma