Phase I/II Study of Pazopanib and Cyclophosphamide in Patients With Platinum-resistant Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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The current trial shall clarify the potential of the multitarget antiangiogenic tyrosinkinase inhibitor GW 786034 (pazopanib) in combination with oral cyclophosphamide as salvage treatment in patients with recurrent, pretreated ovarian cancer.

Detailed Description
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This study is a prospective open-label, non-randomized multicenter phase I/II trial in order to determine overall response rate of patients with platinum-resistant or refractory recurrent, pretreated epithelial ovarian cancer. In order to assure adequate toxicity assessment, a phase-I-trial is proponed. Phase II will be performed with MTD.

Official Title
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A Phase I/II Study of Pazopanib (GW786034) and Cyclophosphamide in Patients With Platinum-resistant Recurrent, Pre-treated Ovarian Cancer

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Drug: Pazopanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Female subjects ≥18 years of age Histologically or cytologically confirmed diagnosis of: epithelial ovarian cancer which is platinum resistant or platinum refractory,cancer of the fallopian tube, peritoneal cancer Patients must have failed available standard chemotherapy regimen Prior treatment with at least 2 chemotherapy regimens in advanced tumor setting Performance status ECOG 0 - 2 Adequate contraception Adequate organ function Measurable disease according to RECIST criteria. Able to swallow and retain oral medication. Life expectancy of at least 12 weeks. Exclusion Criteria: Any second malignancy within the last 5 years, with the exception of basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy). Prolongation of 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 Symptomatic peripheral vascular disease Coronary artery by-pass graft surgery Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA) History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months Macroscopic hematuria Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug Evidence of active bleeding or bleeding diathesis Known endobronchial lesions or involvement of large pulmonary vessels by tumor Prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug. Biological therapy, hormonal therapy or treatment with an investigational agent within 28 days or 5 half-lives Prior antiangiogenic therapy. Is unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. Pregnancy More than 3 different chemotherapy regimens in advanced tumor setting Uncontrolled hypertension History of ischemic event (stroke, myocardial infarction, unstable angina, TIA, symptomatic peripheral vascular disease) History or clinical evidence of thrombo-embolic event History of haemoptysis, cerebral, or clinically significant gastrointestinal haemorrhage in the past 6 months Active bleeding Signs/Suspicion of intestinal obstruction

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Cyclophosphamid + Pazopanib<br>Cyclophosphamid + Pazopanib | Drug: Pazopanib<br>* Phase I Cyclophosphamid Pazopanib Dose level I 50 mg/day 400 mg/day Dose level II 50 mg/day 600 mg/day Dose level III 50 mg/day 800 mg/day Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally Phase II: Cyclophosphamide 50 mg daily orally Pazopanib 400, 600 or 800 mg daily orally The dose for the phase II part of the trial will be based on the MTD of phase I.<br>* Other names: Cyclophosphamid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the optimal doses for pazopanib (phase I) |  | 42 months | 
| Overall response rate according to RECIST criteria / clinical benefit (stable disease or partial response or complete response) (phase II) |  | 12 weeks after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression (TTP) according to RECIST criteria |  | 7 years | 
| Overall survival |  | 7 years | 
| Evaluation of CA125 tumour response |  | 7 years | 
| Number of patients with Adverse Events |  | 7 years | 
| Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire |  | 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer