Pazopanib Maintenance Phase II

Study Overview
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Brief Summary
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This trial compares pazopanib to placebo as maintenance treatment over 2 years in patients with retroperitoneal and visceral high-risk soft tissue sarcomas after multimodal treatment including prior neo- and/or adjuvant doxorubicin / ifosfamide chemotherapy with regional hyperthermia.

Official Title
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A Randomized, Double Blind, Phase II Trial of Pazopanib Versus Placebo as Maintenance Therapy in Patients With Retroperitoneal and Visceral High-risk Soft Tissue Sarcomas Following Prior Neo- and/or Adjuvant Doxorubicin / Ifosfamide Chemotherapy With Regional Hyperthermia

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: Pazopanib
* Drug: Placebo (for Pazopanib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up Patients must have histological evidence of high-grade soft tissue sarcoma (grade 2 - 3) according to the FNLCC grading system, tumor size ≥ 5 cm and deep localization with regard to the superficial fascia, excluding the following tumor types: Embryonal rhabdomyosarcoma Chondrosarcoma (excluding extraskeletal myxoid chondrosarcoma) Osteosarcoma (excluding extraskeletal osteosarcoma) Ewing tumors / primitive neuroectodermal tumor (PNET) Gastro-intestinal stromal tumors (GIST) Dermatofibrosarcoma protuberans Patients who had undergone previous surgery with inadequate margins (tumour-free margins ≤1 cm or margins contaminated) are eligible if thermochemotherapy has been started within 8 weeks after surgery Unstained slides and ideally tumour blocks must be available for histological central review Completed 4 to 8 cycles of thermochemotherapy with doxorubicin and ifosfamide at least 21 days but no more than 42 days prior to study entry No evidence of disease following completion of first-line thermochemotherapy and within ≤ 21 days of study entry Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 No other prior chemotherapy except thermochemotherapy with doxorubicin and ifosfamide Adequate organ system function Exclusion Criteria: No prior or concurrent second primary malignant tumors (except adequately treated in situ carcinoma of cervix, or basal cell carcinoma) No symptomatic or known Central nervous system (CNS) metastases at baseline Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease Known intraluminal metastatic lesion/s with risk of bleeding Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other gastrointestinal conditions with increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: Malabsorption syndrome Major resection of the stomach or small bowel. Corrected QT interval (QTc) > 480 msecs History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (See Appendix D for description) Poorly controlled hypertension (SBP of ≤ 150 mmHg or DBP of ≤95 mmHg is acceptable provided that BP will be treated and monitored at least weekly. The goal is to attain controlled hypertension within 4 weeks of start of IMP which is defined as grade ≤1 hypertension CTCAE Version 4.0) NYHA II at Screening for Patients > 65 years History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery). Evidence of active bleeding or bleeding diathesis. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed. Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed. Recent hemoptysis (≥½ teaspoon of red blood within 8 weeks before first dose of study drug). Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pazopanib<br>800mg, oral, 24 months | Drug: Pazopanib<br> <br> * Other names: Votrient;|
| Placebo Comparator: Placebo<br>800mg, oral, 24 months | Drug: Placebo (for Pazopanib)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) |  | after 58 events have occurred, at the latest 27 month after the final patient is recruited | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | after 58 events have occurred, at the latest 27 month after the final patient is recruited | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high-risk soft tissue sarcoma, pazopanib, retroperitoneal soft tissue sarcoma, visceral soft tissue sarcoma, votrient