Trial Examines Triplet Regimen in Ovarian Cancer

Krishnansu S. Tewari, MD

Krishnansu S. Tewari, MD

A multipronged attack on the tumor vasculature network is at the heart of a recently launched clinical trial aimed at developing new therapeutic options for women with advanced, recurrent, platinum-resistant ovarian cancer. The novel agent fosbretabulin tromethamine is being combined with bevacizumab (Avastin) and physician’s choice of either paclitaxel or pegylated liposomal doxorubicin in the experimental arm of the phase II/III FOCUS study (NCT02641639). The regimen will be compared with bevacizumab plus chemotherapy.

RATIONALE

In the single-arm, phase II, GOG-01861 study, the combination demonstrated a median progression-free survival of 7.3 months compared with 4.8 months for bevacizumab alone and a 35.7% overall response rate versus 28.2%, respectively.

Fosbretabulin and bevacizumab both target vascular signaling but in different ways, explained principal investigator Krishnansu S. Tewari, MD, director of research in the Division of Gynecologic Oncology at the University of California, Irvine. He said the triplet regimen is "very promising" for patients who are particularly in need of new therapies, noting that thus far, only 1 randomized phase III clinical trial in the platinum-resistant ovarian cancer space has met its primary endpoint.

In GOG-01861, the combination did not result in any unexpected signals Tewari said; however, grade 3 hypertension was observed more in the combination arm. Investigators in the FOCUS study will be watching carefully for cardiovascular side effects, including hypertension and sinus tachycardia among patients who receive both vascular-targeting drugs.

TRIAL DESIGN

The FOCUS study will be conducted in 2 stages. In the first part, 80 patients will be randomized to the experimental 3-drug regimen versus the control; up to 4 interim analyses will be conducted so that researchers can determine the safety and efficacy of the novel strategy. The second part of the study will randomize approximately 350 patients to the same treatment arms.

WHO IS ELIGIBLE?

The trial is open to women aged 18 years and older with confirmed platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received ≥1 prior platinum-based regimens and have measurable disease. Participants receiving doxorubicin must have left ventricular ejection fraction ≥45% at baseline assessment.

Mateon Therapeutics, which is sponsoring the FOCUS trial, also is studying the drug in combination with pazopanib in ovarian cancer that is recurrent after platinum-containing therapy.