This is a randomized, two-arm, open-label Phase II multicenter study designed to examine the effects of adding bevacizumab to ixabepilone for the treatment of patients who have recurrent or persistent platinum-resistant/refractory epithelial (non-mucinous) ovarian, fallopian tube, or primary peritoneal cancer. Its primary objective is to assess whether adding bevacizumab to ixabepilone improves progression-free survival in its target population. Study participants will be stratified by (a) study site and (b) previous receipt of bevacizumab prior to randomization.
The primary objective of this study is as follows: * To assess the activity of ixabepilone with bevacizumab compared to ixabepilone alone in patients with recurrent or persistent platinum-resistant/refractory epithelial (non-mucinous) ovarian, fallopian tube, or primary peritoneal cancer. We will assess this by comparing the ixabepilone +bevacizumab (experimental) arm to the ixabepilone-alone (control) arm for an improvement in median progression free survival (PFS). The secondary objectives of this study are as follows: * To compare the experimental arm to the control arm for increases in objective response rate (ORR) and durable disease control rate (DDCR). * To compare the experimental arm to the control arm for an increase in overall survival (OS). * To assess the safety profile of ixabepilone in combination with bevacizumab in ovarian, fallopian tube, or primary peritoneal cancer patients. * To assess whether prior treatment with bevacizumab impacts future response to bevacizumab in combination with ixabepilone. In addition to the primary and secondary objectives of this study, there are additional exploratory/correlative objectives. The exploratory/correlative objectives of this study are as follows: * To characterize number, length and composition (e.g., class III β-tubulin expression) of microtentacles (McTNs) isolated from circulating tumor cells isolated from whole blood of patients undergoing treatment with ixabepilone with or without bevacizumab, and correlate with best response, PFS, and OS. * To observe McTNs on circulating tumor cells in blood using a novel polyelectrolyte multi-layer (PEM) tethering technology. * To correlate ex vivo response of McTNs to drug treatment with clinical response in order to develop a real-time assay to predict response to therapy. * To explore use of circulating tumor (ct) DNA as a biomarker for disease response and compare its performance to CA-125. * To examine whether clinical response to ixabepilone with or without bevacizumab differs between high and low expressors of class III β-tubulin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Ixabepilone will be administered at 20 mg/m2 intravenously days 1, 8, 15 of a 28-day cycle over one hour. Treatment will continue until progression, death, or prohibitive side effects. If any patient has a complete response, patient may stop treatment after 2 additional consolidation cycles following documented complete response
Bevacizumab will be administered at 10 mg/kg intravenously days 1, 15 of a 28-day cycle over one hour. Bevacizumab will be infused after ixabepilone. The first dose of bevacizumab will be administered intravenously over 90 minutes; the second dose may be administered over 60 minutes if no prior reaction to previous infusion; subsequent doses may be administered over 30 minutes if no prior reaction to previous infusion. Treatment will continue until progression, death, or prohibitive side effects. If any patient has a complete response, patient may stop treatment after 2 additional consolidation cycles following documented complete response.
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, United States
Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
Baltimore, Maryland, United States
Progression-free Survival (PFS) Differences Between Ixabepilone Alone and Ixabepilone + Bevacizumab
Progression-free survival (PFS), the primary endpoint, will be defined as the length of time from randomization to disease recurrence, disease progression, or death for any reason. The timeframe was updated upon results entry.
Time frame: Up to 37 months
Objective Response Rate (ORR)
Treatment response will be based on RECIST v1.1 Guidelines for measurable lesions. Objective response rate (ORR) includes evaluation for partial response (PR) or complete response (CR). Time frame was updated upon results entry.
Time frame: Up to 37 months
Overall Survival (OS) Differences Between Ixabepilone Alone and Ixabepilone + Bevacizumab
Overall survival (OS) is defined as time from randomization to death from any cause. Time frame was updated upon results entry.
Time frame: Up to 37 months
Number of Participants With Treatment Related SAEs
Safety profile of Ixabepilone in combination with Bevacizumab as defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Presented are the number of participants that experienced SAE's related to study drug. Full reporting of adverse events is presented in the Adverse Events module. Time frame was updated upon results entry.
Time frame: Up to 37 months
Differences in Response to the Combination of Ixabepilone and Bevacizumab in Relationship to Previous Treatment With Bevacizumab and Taxanes
Assess whether prior treatment with Taxanes impacts future response to Bevacizumab in combination with Ixabepilone. BEST RESPONSE using RECIST Criteria- Complete Response (CR): The disappearance of all target lesions. There should be no evidence of disease, and any pathological lymph nodes must have reduced in size to normal (short axis less than 10 mm). Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesion
Time frame: Up to 41 months
Durable Disease Control Rate (DDCR) Differences Between Ixabepilone Alone and Ixabepilone + Bevacizumab
Treatment response will be based on RECIST v1.1 Guidelines for measurable lesions. Objective response rate (ORR) includes evaluation for partial response (PR) or complete response (CR). Durable Disease Control (DDC) is defined as complete response (CR), partial response (PR), or stable disease (SD) ≥6 months from date of best response. Presented are the counts of those that achieved DDC.
Time frame: 5 Years
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