Marshall Edwards, Inc. announced enrolment of the first patient in Europe in the phase III Ovature clinical trial of phenoxodiol in women with advanced ovarian cancer resistant or refractory to platinum-based drugs.
The first patient to commence on the study at an Ovature site in the EU has been enrolled at the Catholic University of Leuven, Belgium, under the direction of Professor Ignace Vergote, head of gynaecologic oncology.
"We are hopeful that a positive outcome of this multi-centre study will be a significant medical advance for thousands of women with late stage ovarian cancer whose tumours have become insensitive to the existing chemotherapeutic drugs," Professor Vergote said.
"As one of Europe's largest cancer institutions, it is important for us to be a part of these worldwide studies. It is important that we continue to develop new ovarian cancer treatments. It is only through constant research that we will learn how to battle this deadly disease effectively," said Professor Vergote.
The Catholic University of Leuven is one of 26 sites in UK and Europe which will be recruiting patients into this major multi-centre multinational ovarian cancer study to determine the safety and effectiveness of the drug phenoxodiol, when used in combination with the chemotherapy drug, carboplatin. Ovarian cancer patients whose cancer initially responded to chemotherapy, but has since become resistant or refractory to traditional platinum treatments are eligible to participate.
There will be an additional 30 sites in the USA, of which 7 are now recruiting patients, and there are 4 sites open in Australia.
The total number of patients to be treated in this pivotal study is 470. The trial consists of two double blind treatment arms. Patients in one trial arm will receive weekly carboplatin and phenoxodiol. Patients in the other trial arm will also receive weekly carboplatin, but a placebo will be substituted for phenoxodiol. Neither patients, nor their doctors will know to which trial arm the patients are randomised.
A change from receiving carboplatin (or cisplatin) in the traditional dose pattern (every two to three weeks) to a weekly carboplatin regimen has been reported to provide a tumour response in some patients with recurrent ovarian cancer1-3. Thus in addition to learning more about the safety and efficacy of phenoxodiol, researchers will learn more about the efficacy of weekly carboplatin.
The primary outcome of the trial is the assessment of the relative time it takes for the ovarian cancer to progress. An analysis of interim results will be possible after 95 patients have progressed with their disease.
The trial is being run under arrangements approved by the US Food and Drug Administration (FDA) known as a Special Protocol Assessment (SPA). This provides for the interim analysis of the data, which, if significant, can be used to support a request for grant of marketing approval.
The chief executive officer of Marshall Edwards, Inc., Christopher Naughton, said the phase III Ovature study was a significant milestone for the company.
"Over the next 12 to 18 months we expect the interim results from this multi-national clinical trial which may lead to the first approval for phenoxodiol," Naughton said.
In a prior phase II clinical trial, phenoxodiol was tested in combination with either cisplatin or paclitaxel. Patients with late stage ovarian cancer that had become refractory to platinum or paclitaxel therapy, following multiple courses of chemotherapy, were treated with phenoxodiol and cisplatin or phenoxodiol and paclitaxel, respectively. Of 21 patients in the cisplatin arm there were six partial responders, nine patients with stabilised disease and six patients who had disease progression; of 19 in the paclitaxel arm, there was one complete responder, two partial responders, eleven with stabilised disease and five patients who had disease progression. There were few side effects associated with phenoxodiol, but, as with any investigational drug, there is a possibility of unexpected side effects.
Phenoxodiol is being developed as a therapy for late-stage, chemo-resistant prostate, ovarian and cervical cancers. Phenoxodiol is an investigational drug and, as such, is not commercially available. It is a novel-acting drug that inhibits key pro-survival signalling pathways operating via sphingosine-1-phosphate and Akt. Inhibition of these pathways leads to prevention of phosphorylation of key anti-apoptotic proteins such as XIAP. Loss of activity of these proteins restores the ability of chemoresistant tumour cells to undergo apoptosis in response to chemotherapy. The putative molecular target for phenoxodiol is a tumour-specific protein, accounting for the highly selective nature of the drug.
Marshall Edwards, Inc. is a specialist oncology company focused on the clinical development of novel anti-cancer therapeutics. These derive from a flavonoid technology platform which has generated a number of novel compounds characterised by broad ranging efficacy against a range of cancer targets with few side effects. Marshall Edwards, Inc., is majority owned by Novogen, an Australian biotechnology company that is specialising in the development of therapeutics based on a flavonoid technology platform.