419TiP - Chemosensitization of Carboplatin by NOX66 - Pharmacokinetics and Safety

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Clinical research
Basic Scientific Principles
Therapy
Biological therapy
Presenter Ian Minns
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors I. Minns, G. Kelly
  • Clinical Development And Medical Affairs, Noxopharm Limited, 2074 - Sydney/AU

Abstract

Background

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.

Trial design

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

Noxopharm Limited

Funding

Noxopharm Limited

Disclosure

I. Minns: Employee of Noxopharm Limited. G. Kelly: Member of the board of Directors, employee and a shareholder of Noxopharm Limited.