A Phase II, Open-Label Study Evaluating the Effect Of GW786034 In Subjects With Ovarian Cancer

Study Overview
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Brief Summary
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This study was designed to find out how effective and safe GW786034, is in the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer that has not responded to standard treatment.

Official Title
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This Study is a Non-randomized, Open-label, Multi-center Phase II Study of GW786034 to Evaluate the Administration of Oral GW786034 in Subjects With Ovarian Cancer.

Conditions
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Peritoneal Cancer, Ovarian Cancer, Neoplasms, Ovarian, Fallopian Tube Cancer

Intervention / Treatment
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* Drug: GW786034


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Confirmed diagnosis of epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Has received one prior platinum-based chemotherapy regimen(cisplatin,carboplatin, or oxaliplatin). Has psychological, familial, sociological or geographical condition that does not permit compliance with the protocol. Is on a specifically prohibited medication or requires these medications during treatment with GW786034. Exclusion criteria: Has had any surgery, chemotherapy, hormonal therapy, biologic, immunotherapy, or radiotherapy with in the last 28 days and has not recovered from such prior therapy. Poorly controlled hypertension(systolic 140mmHg or higher or Diastolic 90mmHg or higher). Currently taking warfarin. Low molecular weight heparin and low-dose warfarin(1mg per day)is permitted.

Ages Eligible for Study
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Minimum Age: 21 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib<br>800 mg GW786034 administered orally on a daily basis. | Drug: GW786034<br>* 800 mg GW786034 administered orally on a daily basis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Biochemical Response (Cancer Antigen [CA-125]) | Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: 50% response=≥50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments) then confirmed after 21 days. 50% CA-125 response was normalized (CA-125 >21U/mL) or non-normalized (CA-125≤1U/mL). Progressive disease (PD) =CA-125 increase ≥100% from nadir (nadir >21U/mL) or ≥42U/mL (nadir ≤21U/mL); nadir was lowest CA-125. PD was confirmed after 21 days; otherwise=unconfirmed PD. Stable disease=scenarios that do not meet 50% response or PD. CA-125 response rate was defined as % of participants with 50% response. | Baseline to response (up to 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Biochemical Response (CA-125) | Time to biochemical response was calculated as the date pazopanib was first dosed to the date CA-125 was first reduced by 50% or greater. The reduction in CA-125 of 50% or greater was to be confirmed by a repeat measurement (no earlier than 21 days after initial evaluation documenting decrement). This was calculated for all participants with confirmed CA-125 50% reduction. | Baseline to response (up to 3 years) | 
| Duration of Biochemical Response (CA-125) | Calculated as the date of confirmed first 50% or greater reduction in CA-125 to date of documented progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest. This was calculated for all participants with confirmed CA-125 50% reduction. | Baseline to response (up to 3 years) | 
| CA-125 Doubling Time Prior to and During Treatment With Pazopanib | CA-125 doubling time is defined as the time for CA-125 to double from baseline value. This measure was not reported, as no participants had a post-baseline CA-125 that was double the baseline value. Therefore, the data did not warrant a report. | Baseline to doubling of CA-125 (up to 3 years) | 
| Overall Response and Stable Disease (SD) | Overall response and stable disease (SD) are based on biochemical, radiographic, and clinical assessments according to the modified criteria of Gynecologic Cancer Intergroup (GCIG) (see primary outcome). Response is presented as the percentage of participants with the given response. | Baseline to response (up to 3 years) | 
| Median Progression-free Survival (PFS) | Progression-free survival analysis was performed on all participants and then stratified by CA-125 response status (having confirmed 50% reduction or not). PFS was defined as the time from the date of the first dose of study drug to the date of documented and confirmed progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest, or to date of death due to any causes. | Date of the first dose of study drug to the date of documented and confirmed progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest, or to date of death due to any causes (up to 2 years) | 
| Overall Tumor Response | Overall tumor response following daily administration of pazopanib was defined using radiographic assessments based on Response Evaluation Criteria for Solid Tumors (RECIST) criteria for subjects with measurable disease at baseline. | Baseline to response (up to 3 years) | 
| Number of Participants With the Indicated Maximum Shift From Baseline (BL) in Diastolic Blood Pressure | Summary of shifts in diastolic blood pressure from baseline to the maximum change in the study. mmHg, millimeters of mercury. | Baseline to response (up to 3 years) | 
| Number of Participants With the Indicated Maximum Shift From Baseline (BL) in Systolic Blood Pressure | Summary of shifts in systolic blood pressure from baseline to the maximum change in the study. mmHg, millimeters of mercury. | Baseline to response (up to 3 years) | 
| Number of Participants With the Indicated Maximum Shift From Baseline (BL) in Heart Rate | Summary of shifts in heart rate from baseline to the maximum change in the study. bpm, beats per minute. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Albumin | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Amylase and Lipase | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Total Bilirubin and Creatinine | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Calcium, Glucose, Potassium, Sodium, and Urea | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Thyroxine | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Thyroid Stimulating Hormone | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Hemoglobin and Hematocrit | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 
| Mean Change From Baseline to Response in Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pazopanib, Fallopian tube cancer, Ovarian epithelial cancer, Peritoneal cancer