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

NCT02641639 | Terminated Phase 2 Results DMC

• 1 other identifier: OX4325
• Study Type: interventional
• Target: 70
• Locations: 3 countries
• Sites: 40

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.

Conditions

Platinum Resistant Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  12 Months

Secondary Outcomes (4)

• Improvement in Objective Response Rate

  12 Months

• Overall Survival (OS)

  12 Months

• Proportion of Subjects Who Remain Progression-free at 12 Months

  12 Months

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of PCC Plus Bevacizumab and CA4P Versus PCC Plus Bevacizumab and Placebo

  12 Months

Study Arms (2)

Fosbretabulin tromethamine

ACTIVE COMPARATOR

Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin \[PLD\]) plus bevacizumab and CA4P

Drug: Fosbretabulin tromethamine

Placebo

PLACEBO COMPARATOR

Physician's choice chemotherapy (weekly Paclitaxel or Pegylated Liposomal Doxorubicin \[PLD\]) plus bevacizumab and placebo

Drug: Placebo

Interventions

Fosbretabulin tromethamine DRUG

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.

Also known as: Fosbretabulin Combretastatin A4-Phosphate, CA4P

Fosbretabulin tromethamine

Placebo DRUG

Saline for infusion

Also known as: Saline for infusion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF)
• Age ≥ 18 years (Age ≥ 19 years if required by local regulatory authorities)
• ECOG PS of 0-1
• Histologically or cytologically-confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer in recurrent stage
• prOC (platinum-resistant ovarian cancers) defined as progression within \> 1 to \< 6 months (+ 2 weeks) of completing previous cycle of primary platinum-based therapy, or during or within \< 6 months (+ 2 weeks) of starting additional platinum based therapies
• Received ≥ 1 but ≤ 3 prior platinum-based regimens
• Measurable disease according to RECIST 1.1
• Left ventricular ejection fraction (LVEF) greater than or equal to at least 45% at baseline assessment if subject is receiving PLD, and/or anthracycline is a concomitant medication
• No evidence of active (progressing) brain metastasis. (Treated brain metastasis allowed with a posttreatment magnetic resonance imaging (MRI) or Computed Tomography (CT) of brain showing no active (progressing) brain metastasis). Treatment of brain metastasis may include surgery, radiosurgery (linear accelerator (LINAC), gamma knife), or whole brain irradiation. Surgery for brain metastasis must be \> 8 weeks from study entry
• Hemoglobin \> 9 g/dl. Erythroid growth factors should not have been used in the 2 weeks prior to study entry. Red blood cell transfusions are permitted to maintain the hemoglobin level \> 9 g/dl
• Adequate bone marrow function in the investigator's opinion
• Adequate hepatic function defined by the following:
• Total bilirubin \< 2 x Upper Limit of Normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 X ULN for the referenced lab (\< 5 X ULN for subjects with liver metastases)
• Adequate renal function defined by the following:

You may not qualify if:

• Subjects who have received prior CA4P therapy
• Previously having failed treatment with bevacizumab combined with the intended PCC.
• \- For clarity: Investigators should not select a bevacizumab + PCC combination for the FOCUS trial if the patient has previously failed that same regimen, however they may select a new PCC regimen to combine with bevacizumab. For example, a patient who failed bevacizumab + weekly paclitaxel would be allowed to enroll in FOCUS only if they are assigned to bevacizumab + PLD for the study.
• Previous treatment with greater than three traditional chemotherapy treatment regimens
• Untreated brain metastasis or leptomeningeal brain metastasis
• Solid organ or bone marrow transplant
• Primary platinum-refractory disease (defined as progression during dosing or within one (1) month of completing the last cycle of patients first platinum-containing regimen)
• \> Grade 2 peripheral neuropathy
• Current thrombotic or hemorrhagic disorder/event or history of prior event within 6 months of start of Screening
• History of prior cerebrovascular event, (including transient ischemic attack) within 6 months of start of Screening
• Recent history (within 6 months of start of Screening) of angina pectoris, myocardial infarction (including non-Q wave MI), or NYHA Class III and IV congestive heart failure
• History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\<60 bpm), heart block (excluding 1st degree block, benign PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
• Known uncontrolled HIV infection
• Uncontrolled, clinically significant active infection
• Serious non-healing wound, ulcer or bone fracture

Sponsors & Collaborators

• Mateon Therapeutics: lead

Study Sites (40)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35249, United States

Location

Mitchell Cancer Institute - USA Health System

Mobile, Alabama, 36604, United States

Location

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85016, United States

Location

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85711, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Oncology Institute of Hope and Innovation

Lynwood, California, 90262, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

California Pacific Medical Center, Research Institute

San Francisco, California, 94115, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Rocky Mountain Cancer Centers, LLP

Lakewood, Colorado, 80228, United States

Location

Hartford Health Care Cancer Institute; Affiliate Memorial Sloan Kettering

Hartford, Connecticut, 06102, United States

Location

Stamford Hospital - Bennett Cancer Center

Stamford, Connecticut, 06904, United States

Location

Sylvester Comprehensive Cancer Center University of Miami

Miami, Florida, 33136, United States

Location

Baptist Health Medical Group Oncology, LLC

Miami, Florida, 33176, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Maine Medical Center

Scarborough, Maine, 04074, United States

Location

Mercy Medical Center; The Institute for Cancer Care

Baltimore, Maryland, 21202, United States

Location

HCA Midwest Division - Sarah Cannon Cancer Institute

Kansas City, Missouri, 64132, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Oklahoma Heath Sciences Center - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Tulsa Cancer Institute

Tulsa, Oklahoma, 74146, United States

Location

OHSU Center for Women's Health & Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Willamette Valley Cancer Institute

Springfield, Oregon, 97477, United States

Location

Lehigh Valley Hospital, John and Dorothy Morgan Cancer Center; Affiliate Memorial Sloan Kettering

Allentown, Pennsylvania, 18103, United States

Location

The Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Gibbs Cancer Center & Research Institute Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78731, United States

Location

Texas Oncology

Bedford, Texas, 76022, United States

Location

Dallas County Hospital District d/b/a Parkland Health and Hospital System

Dallas, Texas, 75235, United States

Location

Simmons Comprehensive Cancer Center; UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75246, United States

Location

Texas Oncology San Antonio

San Antonio, Texas, 78229, United States

Location

Texas Oncology, P.A.

The Woodlands, Texas, 77380, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

UZ Leuven

Leuven, Belgium

Location

Universitätsklinikum Erlangen

Erlangen, D-91054, Germany

Location

Universitätsklinikum Essen (AöR) Klinik für Frauenheilkunde und Geburtshilfe

Essen, 45147, Germany

Location

Universitäts-Frauenklinik Dept. für Frauengesundheit

Tübingen, 72076, Germany

Location

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: CEO
• Organization: Mateon Therapeutics Inc

ir@oncotelic.com

(650) 635-7000

Study Officials

• Harish Dave, MD

  Medical Monitor

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: December 29, 2015
• Study Start: June 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: March 24, 2025
• Results First Posted: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); US (36); DE (3)