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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
70
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.
Saline for infusion
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States
Mitchell Cancer Institute - USA Health System
Mobile, Alabama, United States
Arizona Oncology Associates, PC - HAL
Phoenix, Arizona, United States
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, United States
University of Arizona Cancer Center
Tucson, Arizona, United States
Progression Free Survival
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.
Time frame: 12 Months
Improvement in Objective Response Rate
Improvement in objective response rate (ORR). The ORR will be defined as the proportion of subjects with a confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1 criteria, based upon the best response. The ORR will be determined based on investigator assessment according to RECIST 1.1 criteria and/or GCIG CA-125 criteria.
Time frame: 12 Months
Overall Survival (OS)
Evaluation of overall survival (OS)
Time frame: 12 Months
Proportion of Subjects Who Remain Progression-free at 12 Months
Assessment of the proportion of subjects who remain progression-free at 12 months on the regimen of PCC plus bevacizumab and CA4P compared with PCC plus bevacizumab and placebo
Time frame: 12 Months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo
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.
Time frame: 12 Months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Oncology Institute of Hope and Innovation
Lynwood, California, United States
University of California Irvine
Orange, California, United States
California Pacific Medical Center, Research Institute
San Francisco, California, United States
Sansum Clinic
Santa Barbara, California, United States
Rocky Mountain Cancer Centers, LLP
Lakewood, Colorado, United States
...and 30 more locations