FOCUS: PCC + Bevacizumab + CA4P Versus PCC + Bevacizumab + Placebo for Subjects With Platinum Resistant Ovarian Cancer

Phase 2

Terminated

Conditions: Platinum Resistant Ovarian Cancer

Interventions: Drug: Placebo
Drug: Fosbretabulin tromethamine

Registration Number: NCT02641639

Lead Sponsor: Mateon Therapeutics

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin \[PLD\]) plus bevacizumab and placebo
Fosbretabulin tromethamine	Fosbretabulin tromethamine	Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin \[PLD\]) plus bevacizumab and CA4P

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	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.

Secondary Outcome Measures

Name	Time	Method
Improvement in Objective Response Rate	12 Months	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.
Overall Survival (OS)	12 Months	Evaluation of overall survival (OS)
Proportion of Subjects Who Remain Progression-free at 12 Months	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
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo	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.

Trial Locations

Locations (37): University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
Mitchell Cancer Institute - USA Health System
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Mobile, Alabama, United States
Arizona Oncology Associates, PC - HAL
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Phoenix, Arizona, United States
Arizona Oncology Associates, PC - HOPE
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Tucson, Arizona, United States
University of Arizona Cancer Center
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Tucson, Arizona, United States
Oncology Institute of Hope and Innovation
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Lynwood, California, United States
University of California Irvine
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Orange, California, United States
California Pacific Medical Center, Research Institute
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San Francisco, California, United States
Sansum Clinic
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Santa Barbara, California, United States
Rocky Mountain Cancer Centers, LLP
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Lakewood, Colorado, United States
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University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States