The U.S. Food and Drug Administration (FDA) has cleared a Phase 2b clinical trial to evaluate the effects of combining SUBA-Itraconazole, an oral anti-fungal medication with anti-cancer properties, with chemotherapy for treating men with metastatic castration-resistant prostate cancer (mCRPC) who responded poorly to prior therapies.
The FDA accepted the investigational new drug (IND) application filed by Inhibitor Therapeutics and the company’s design of the randomized, double-blind, placebo-controlled Phase 2b trial, called PREDICT.
PREDICT will evaluate the effectiveness and safety of SUBA-Itraconazole capsules given in combination with standard chemotherapy (docetaxel and prednisone) in men with mCRPC.
Approximately 23,000 men in the U.S. are diagnosed each year with late-stage mCRPC that no longer responds to standard hormone therapy to lower the levels of male hormones, nor to chemotherapy or newer hormone therapies such as Xtandi (enzalutamide), Zytiga (abiraterone), or Erleada (apalutamide).
PREDICT will determine SUBA-Itraconazole’s potential to treat these patients whose disease has progressed or who have stopped other therapies due to toxicity or other reasons.
The trial’s primary efficacy measure will be improvements in patients’ progression-free survival — the length of time until disease progression, assessed on radiography scans, or death. The study will be conducted across six countries in North America and Europe.
“I am pleased to announce that we have received IND clearance for our PREDICT trial,” Nicholas J. Virca, Inhibitor’s president and CEO, said in press release. “FDA … indicated that the general design and planned analysis of our study would adequately address the objectives necessary to support an eventual New Drug Application (NDA) submission for this indication.
“FDA also indicated that the final analysis of the key secondary endpoint of overall survival (OS) can occur following submission of the NDA for approval in the United States,” he added.
SUBA-Itraconazole, manufactured by Mayne Pharma (a major shareholder of Inhibitor), is an FDA-approved medication used to treat serious fungal infections. It consists of an oral formulation of itraconazole that improves its absorption in the body and leads to more stable levels in the bloodstream than with the generic formulation of itraconazole. This enables a more predictable clinical dose response and the use of lower treatment doses.
In addition to its anti-fungal properties, itraconazole also appears to have promising anti-cancer effects, which have been shown in brain tumors in animal models and in basal cell carcinoma, lung, and prostate cancers in human trials.
Itraconazole blocks a protein receptor called smoothened, or SMO, which provides signals for the activation of a pathway called Hedgehog.
Research indicates that inhibiting Hedgehog could delay or possibly prevent the development of certain cancers in humans. Oral inhibitors of the pathway, including Erivedge (vismodegib, by Genentech) and Odomzo (sonidegib, by Novartis), have actually been approved for the treatment of basal cell carcinoma, a type of skin cancer.
In a previous Phase 2 trial (NCT02354261) conducted by Inhibitor, SUBA-Itraconazole was found to suppress this type of cancer without causing the side effects typically associated with Hedgehog inhibitors, suggesting it could be a safer therapy for slowing the progression of cancer.