Phase II randomized clinical trial of Pazopanib alone and Pazopanib plus Gemcitabine in relapsed or metastatic soft tissue sarcoma

INTERVENTION: Trade Name: Votrient 400 mg film‐coated tablets Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: PAZOPANIB CAS Number: 444731‐52‐6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 800‐ Product Name: Gemcitabine Product Code: Gemcitabine Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: GEMCITABINE CAS Number: 95058‐81‐4 Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 1000‐ Trade Name: Votrient 200 mg film‐coated tablets Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: PAZOPANIB CAS Number: 444731‐52‐6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 800‐ CONDITION: Relapsed or metastatic soft tissue sarcoma ; MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: The primary objective of this phase II trial is to assess the efficacy and toxicity of pazopanib alone or pazopanib plus gemcitabine in patients with refractory or relapsed metastatic soft tissue sarcoma (STS). Primary end point(s): Efficacy of the drugs shown by Progression Free Survival Rate at 12 weeks. The Progressive Free Survival Rate at 12 weeks will be determined by the proportion of patients being alive without progressive disease 12 weeks after randomization. Secondary Objective: Secondary objectives are safety and tolerability of the treatment as well as overall survival, time to progression, response rate and quality of life.; Timepoint(s) of evaluation of this end point: 12 weeks after randomization SECONDARY OUTCOME: Secondary end point(s): • Overall survival (OS) ; • Time to Progression (TTP) ; • Response Rate (CR+PR+SD) ; • Toxicity (CTCAE, version 4.0) ; • Quality of live (EORTC) ; Timepoint(s) of evaluation of this end point: In this trial, a “treatment period” will be defined as 21 days. ; ; Overall survival, Toxicity and Quality of life assessment will be performed on day 1 and day 8 of each cycle. ; ; After 6 weeks, accordingly after 2 admitted cycles, and before starting third cycle patients will have documentation of disease status (CT/MRI) to evaluate Response Rate and Time to Progression. CT or MRI will be repeated afterwards every 8 weeks until progression. ; ; After progression, patients will be followed every 3 months ± 28 days until death. The investigator will record disease status, toxicities, quality of life and patient survival. INCLUSION CRITERIA: 1. Histologically or cytological confirmed malignant soft tissue sarcoma including any subtypes except: o Chondrosarcoma o Osteosarcoma o Ewing tumors and primitive neuroectodermal tumors o Gastrointestinal stromal tumors o Dermofibromatosis sarcoma protuberans o Inflammatory myofibroblastic sarcoma o Malignant mesothelioma o Mixed mesodermal tumors of the uterus 2. Patient must have received at least one prior chemotherapy including either an antrazyclin or ifosfamide or both. 3. ECOG performance status 0‐2 4. At least 18 years old 5. Life expectancy > 3 months 6. Patients with at least one measurable lesion according to RECIST criteria (v1.1) 7. Able to swallow and retain oral medication 8. Adequate organ function as defined in protocol 9. A female is eligible to enter and participate in this study if she is either of non childbearing potential (defined in protocol) or childbearing potential with