FOCUS: PCC + Bevacizumab + CA4P Versus PCC + Bevacizumab + Placebo for Subjects With Platinum Resistant Ovarian Cancer
|Platinum Resistant Ovarian Cancer||Drug: Fosbretabulin tromethamine Drug: Placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||FOCUS: A Multicenter, Multinational, Double-Blind, 2-Arm, Randomized, Phase 2/3, Study of Physician's Choice Chemotherapy ([PCC] Weekly Paclitaxel or Pegylated Liposomal Doxorubicin [PLD]) Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo for Subjects With Platinum-Resistant, Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer|
- Progression free survival [ Time Frame: Minimum 12 months ]The primary efficacy parameter in this study is statistically meaningful PFS, defined as the time from the date of randomization until patient discontinuation or death from any cause.
- Improvement in objective response rate [ Time Frame: Minimum 12 Months ]Improvement in objective response rate (ORR), using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Gynecologic Cancer Intergroup (GCIG) cancer antigen-125 (CA-125) criteria
- Evaluation of overall survival (OS) [ Time Frame: Minimum 12 Months ]Evaluation of overall survival (OS)
- Proportion of subjects who remain progression-free at 6, 9, and 12 months [ Time Frame: Minimum 12 Months ]Assessment of the proportion of subjects who remain progression-free at 6, 9, and 12 months on the regimen of PCC plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo
- Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo [ Time Frame: Minimum 12 Months ]To evaluate the Incidence of Treatment-Emergent Adverse Events of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo as measured by aggregate reporting of the number of patient with abnormal findings on (physical exams, vital signs, laboratory measures, ECG, Eastern Cooperative Oncology Group (ECOG) performance status (PS)) and/or analysis of the incidence of adverse events (AEs) using the National Cancer Institute (NCI)-Common Terminology Criteria for AEs (CTCAE) version 4.03.
|Actual Study Start Date:||June 2016|
|Estimated Study Completion Date:||July 2018|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Active Comparator: Fosbretabulin tromethamine
Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin [PLD]) plus bevacizumab and CA4P
Drug: Fosbretabulin tromethamine
CA4P is a synthetic phosphorylated prodrug of CA4, a naturally occurring derivative of the South African willow tree, combretum caffrum. CA4P targets pre-existing tumor vasculature, resulting in an acute, reversible reduction in TBF that leads to central necrosis within tumors.
Other Name: Fosbretabulin Combretastatin A4-Phosphate, CA4P
Placebo Comparator: Placebo
Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin [PLD]) plus bevacizumab and placebo
Saline for infusion
Other Name: Saline for infusion
This is a multicenter, multinational, randomized, double-blind, 2-arm, parallel-group, Phase 2/3 study to evaluate the efficacy and safety of PCC plus bevacizumab and CA4P versus PCC plus bevacizumab and placebo in subjects with platinum-resistant ovarian cancers (prOC). Subjects with platinum-resistant, recurrent, epithelial ovarian, primary peritoneal or fallopian tube cancer will be randomized 1:1 to receive PCC plus bevacizumab and CA4P or PCC plus bevacizumab and placebo. Subjects will be stratified by selected chemotherapy (PLD vs. paclitaxel), platinum free interval (< 3 vs. 3 to 6 months from last platinum therapy to subsequent progression), and line of therapy (2nd vs. 3rd). This is a 2-part study, consisting of a Phase 2, exploratory study (Part 1) followed by a Phase 3, pivotal study (Part 2). Both parts of the study will have similar overall design. Approximately 80 subjects will be randomized into Part 1 and approximately 356 subjects will be randomized into Part 2.
All subjects randomized will receive bevacizumab 10 mg/kg intravenously (IV) on Days 1 and 15, repeated every 4 weeks (q4wk) and PCC with paclitaxel 80 mg/m2 IV on Days 1, 8, 15 and 22, repeated q4wk, or paclitaxel 80 mg/m2 IV on Days 1, 8, 15, repeated q4wk or PLD 40 mg/m2 IV on Day 1, repeated q4wk. Subjects in the Treatment Arm will also receive CA4P 60 mg/m2 on the same day as bevacizumab (Days 1 and 15, repeated q4wk), while subjects in the Control Arm will receive placebo on those days.
Order of dosing will follow the guidance listed below during this study when bevacizumab and CA4P / Placebo are dosed the same day as PCC,
- Bevacizumab followed by CA4P / Placebo followed after 1-3 hours by paclitaxel,
- PLD followed by bevacizumab followed by CA4P / Placebo Subjects will continue randomized treatment until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or sponsor discontinues study for any reason. Subjects will undergo tumor assessments (RECIST) at baseline and every 8 weeks and CA-125 levels at baseline and every 4 weeks.
The primary endpoint is PFS. Secondary endpoints include ORR, OS, proportion of subjects who remain progression free at 6, 9, and 12 months, and safety. Endpoints will be compared between the Treatment Arm and the Control arm. The study duration is estimated to last approximately 3 years.
This study will have 2 parts with the same overall design. Part 1 will enroll up to approximately 80 subjects and will include multiple interim analyses to test the safety and efficacy assumptions in this specific subject population. Upon meeting certain efficacy criteria in Part 1, the protocol will be amended and additional sites added in order to enroll an additional 356 subjects into Part 2 of the study. Subjects enrolled in Part 2 will be analyzed separately and used as a stand-alone confirmatory efficacy study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02641639
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|Study Director:||Harish Dave, MD||Medical Monitor|