Bevacizumab With Abraxane in Patients With Recurrent Ovarian/ Peritoneal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and tolerability of the combination of bevacizumab and Abraxane in the treatment of women with epithelial ovarian cancer or peritoneal cancer. The study will also evaluate how the patient's quality of life is during their treatment.

Official Title
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A Phase 2 Study of Bevacizumab With Abraxane in Patients With Recurrent, Platinum-Resistant Primary Epithelial Ovarian or Primary Peritoneal Carcinoma

Conditions
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Epithelial Ovarian Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Abraxane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable disease by CT or MRI. At least 1 target lesion to be used to assess response as defined by GOG RECIST criteria. ECOG performance status of 0 or 1. Patient provides voluntary written informed consent. At least 18 years of age. Negative serum pregnancy test. Recovered from any recent surgery for at least 30 days and is free of active infection. Received the following prior therapy at time of enrollment: Must have had 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin or organoplatinum. Initial therapy may have included high-dose therapy, consolidation, or extended therapy. Patient should be defined as recurrent or progression of disease within 6 months of last platinum chemotherapy. May have had 1 additional cytotoxic or non-cytotoxic chemotherapy regimen. Must have adequate hematologic and hepatic function. Exclusion Criteria: Previously received bevacizumab. History of other invasive malignancy with the exception of nonmelanoma skin cancer. ECOG performance status of 2, 3, or 4. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study. Patient must be bevacizumab naïve. Blood pressure of >150/100 mm Hg on antihypertensive medications. Prior history of hypertensive crisis or hypertensive encephalopathy. Diagnosed with unstable angina per NYHA or Grade 2 or greater congestive heart failure. History of myocardial infarction within 6 months of enrollment. History of stroke or transient ischemic attack within 6 months prior to study enrollment. Clinically significant vascular disease (e.g., aortic aneurysm, aortic dissection)or symptomatic peripheral vascular disease. Bleeding diathesis or coagulopathy. Presence of CNS or brain metastases. Pre-existing peripheral neuropathy of Grade ≥ 2. A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study. A partial or complete small or large bowel obstruction demonstrated radiologically within 3 months prior to study enrollment. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment. Positive pregnancy test or is lactating. History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to study enrollment. Serious, non-healing wound, ulcer, or bone fracture. Serious intercurrent medical or psychiatric illness, including serious active infection. Inability to comply with study and/or follow-up procedures. Life expectancy of less than 12 weeks. Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible). Known hypersensitivity to any component of bevacizumab.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Bevacizumab|Bevacizumab will be given via IV infusion at 10mg/kg given on days 1 and 15 of a 28-day cycle.|
|Drug: Abraxane|Abraxane will be given via IV infusion at 100mg/m²over 30 minutes on days 1, 8, and 15 of a 28-day cycle.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Progression-Free Rate | Progression-free rate is defined as the percentage of participants with no progression event at 6 months after starting study treatment. An event for this endpoint was defined as a progression-free survival event occurring earlier than six months, or discontinuation of treatment earlier than six months for any other reason. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. | 6 months after initiation of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response | Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR. | Radiologic imaging was repeated after every 3 cycles (about every 12 weeks) during study treatment, up to 31 months. | 
| Overall Survival |  | Overall survival is defined as the time from treatment start until death from any cause, assessed up to 40 months. | 
| Progression-free Survival (PFS) | Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. | PFS was measured from day 1 of treatment until time of progression (assessed every 12 weeks) or death, whichever came first, assessed up to 30 months. | 
| Best Overall Response at Six Months | The outcome measure assessed the percentage of participants who had achieved either a Partial or Complete Response over 6 months of treatment. Radiologic imaging was scheduled to be performed at baseline, after every third treatment cycle, and at the end of treatment or time of progression unless it was done in the previous four weeks. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR+PR. | Assessed over 6 months of study treatment |