The experimental anti-cancer drug, idronoxil, is a selective inhibitor of PI3K/AKT in tumor cells, with studies showing it to be a potent chemosensitizing agent of carboplatin in vitro and in animal studies across a wide range of cancer cell types. These results, however, have not translated to clinical efficacy, with a Phase 3 study of combined oral idronoxil and intravenous carboplatin in patients with late-stage platinum-refractory ovarian cancer discontinued with no efficacy seen. This lack of efficacy is now thought to be due to complete conversion of idronoxil to bio-inactive Phase 2 metabolites. NOX66 is a suppository formulation of idronoxil designed to protect the drug from Phase 2 metabolism. This first-in-human study will look at the ability of NOX66 to deliver relatively high levels of idronoxil in a bio-active form, investigating (a) PK and (b) safety of NOX66 administration both as a monotherapy and in combination with carboplatin.
This is an open label, Phase 1 PK and safety study of NOX66 as a monotherapy and in combination with carboplatin. Patients included have end stage, refactory solid tumours, and no further therapy options available. A total of 16 patients will be recruited into the study in two cohorts of 8 patients. NOX66 suppositories are formulated using 400mg of idronoxil per 2.2g suppository. Patients are allocated to receive either one or two suppositories per day. Study Part 1: NOX66 PK: Patients receive NOX66 for 14 consecutive days as monotherapy, with a follow up period of 7 days post-dosing. Blood samples will be collected throughout the monotherapy arm to measure levels of idronoxil. If no significant adverse events are noted in this 21 day period, a patient will continue in the study. Study Part 2: NOX66 plus Carboplatin: Patients receive NOX66 at the same dose as in Part 1, for 7 days. Carboplatin is administered on Day 2 of treatment. Up to 6 cycles of chemotherapy are administered, at intervals of 28 days. For Cycles 1-3, low dose (AUC4) carboplatin is administered. Subject to safety review, standard dose (AUC6) carboplatin is administered for cycles 4-6. Safety assessment is continued throughout the study, with measures to identify efficacy signals (CT scan, ECOG) performed at baseline and after Cycles 3 and 6.
Clinical trial identification
Trial Protocol Number: NOX66-001A Clinicaltrials.gov NCT02941523
Legal entity responsible for the study
I. Minns: Employee of Noxopharm Limited. G. Kelly: Member of the board of Directors, employee and a shareholder of Noxopharm Limited.