For general questions about clinical trials, visit http://clinicaltrials.gov/ct/info/resources.

1) Where are the sites?
The OVATURE trial is being conducted at clinical sites in the USA, UK, Belgium, Poland, Spain, Italy and Australia. A complete list of all sites participating in the OVATURE trial and each sites’ contact details can be found by going to www.clinicaltrials.gov and typing OVATURE in the search box.

2) Can I participate if a trial site is not nearby?
Each participating site has a study coordinator who can speak with you about making plans to stay near their facility. Contact the investigator listed at the link provided above. You can also check back to that list as additional sites are opening regularly.

3) Does this trial have a placebo arm?
ALL patients on the trial will receive an experimental treatment regimen consisting of weekly carboplatin. Half of the patients in the trial will also receive the investigational drug phenoxodiol. The other half will receive a placebo in place of the phenoxodiol so that neither researchers nor patients can tell which arm the patient is in.

A change from receiving carboplatin (or cisplatin) every second to third week to a weekly carboplatin regimen has been reported to provide a tumor response in some heavily pre-treated patients with recurrent ovarian cancer.¹ In addition to learning more about the safety and efficacy of phenoxodiol, researchers will learn more about the efficacy of weekly carboplatin.

4) How long would I be receiving treatment?
You will receive carboplatin intravenously (IV) once a week and will take two capsules of either phenoxodiol or a placebo orally every eight hours for 28 days. This is one cycle. After two cycles (eight weeks), scans will be repeated to see if you are responding to treatment.

If you are responding and your tumor is getting smaller or staying the same size and you are tolerating the treatment, you will remain on the medication and continue the treatment schedule. Your study doctor will decide for how long this schedule will be continued.

If your tumor grows during the trial (known as “disease progression”), your participation in the study will end and your doctor will discuss further treatment options with you.

Treatment will also stop if you have unacceptable side effects, or if you decide not to have further therapy.

5) What are the chances of success?
Your doctor or the investigator on the trial is best suited to answer questions about each patient’s prognosis.

6) What do researchers know about phenoxodiol?
In laboratory studies using human cancer cell lines in the test tube and in animal models, phenoxodiol was shown to reverse chemoresistance to standard chemotherapies, including platinum drugs, taxanes, gemcitabine, topotecan and doxorubicin. The ability of phenoxodiol to reverse multi-drug resistance is thought to be due to its disruption of several key targets specific to tumor cell survival.

In humans, phenoxodiol was tested for safety first in its IV form. In the Phase I trial, 41 women with platinum- and/or taxane-resistant tumors were given phenoxodiol by drip IV on two consecutive days per week for 12 weeks. One group of the women received 1 mg/kg, one group received 3 mg/kg, another group received 10 mg/kg, and the last group received 20 mg/kg pf phenoxodiol.

The best response in the Phase I trial was stable disease, as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) in four out of 41 women (10 percent of women at three months). No objective evidence of tumor shrinkage was observed. The median length of phenoxodiol therapy was 12 weeks.

In the Phase II trial, phenoxodiol was tested in combination with either cisplatin or paclitaxel. Twenty one patients with late stage ovarian cancer that had become refractory to platinum (cisplatin or carboplatin) and 19 patients that had become resistant to paclitaxel therapy, following multiple courses of chemotherapy, were treated with phenoxodiol and cisplatin or phenoxodiol and paclitaxel respectively. The cisplatin (40 mg/m²) and paclitaxel (80 mg/m²) was administered weekly and phenoxodiol was administered by IV at 3 mg/kg on two consecutive days immediately prior to the cisplatin administration. Treatment was for six weeks and was continued until dose limiting toxicity or disease progression. In this trial, as measured using the RECIST criteria, in the cisplatin arm there were six partial responders, nine patients with stabilized disease and six patients who had disease progression; in the paclitaxel arm, there was one complete responder, two partial responders, eleven with stabilized disease and five patients who had disease progression. For more information about RECIST, visit www.recist.com.

 7) How does phenoxodiol work?
The molecular target for phenoxodiol is believed to be an electron transfer pump mechanism that functions across the cell plasma membrane. This pump is under the control of an NADH oxidase enzyme on the cell surface. Human tumor cells express a variant of this protein and phenoxodiol binds to and inhibits this surface oxidase.

When phenoxodiol inhibits the NADH oxidase, an irreversible cascade of events occurs, resulting in decreased levels of a pro-survival messenger in cells known as S-1-P, which stands for sphingosine-1-phosphate. Platinum resistance is thought to be associated with increased intracellular content of this messenger. Hence removal of this pro-survival signal causes the tumor cell to die. Phenoxodiol removes S-1-P in tumor cells, thereby inducing the tumor cell to undergo apoptosis, or programmed cell death.

8) Have women in other phenoxodiol trials ever become ill from phenoxodiol?
As with any new drug there is a possibility of unexpected side effects associated with the study medication, phenoxodiol, although phenoxodiol has produced few side effects in animals and in previous human trials. If you qualify for the trial, the patient information will be provided to you including the information on potential side effects of the study treatment. Once you read it you will have the opportunity to discuss it with the study doctor if you have any questions about any side effects.

In previous studies, phenoxodiol did not increase the toxicity of other chemotherapy drugs. Nonetheless, phenoxodiol use in combination with standard chemotherapy drugs may lead to the side effects known to be associated with these drugs.

Question not answered here? E-mail us at info@ovaturetrial.com