DR. CHRISTIAN: Our next speaker is Judy Wolf, who is going to describe the phase II trials among the ovarian SPORE programs.

TOP

Thank you. Since I am the very last speaker of the day, hopefully I will be fairly short, because I think that a lot of the issues that we face in the SPOREs have already been raised earlier today, but the ones I think particular face us, I will mention again.

In overview, I want to just go again over the purpose of the SPORE grants, the current trials that are open, the funding of the trials that are open and how they are funded, the regulatory issues that we face, and potential areas for collaboration, and then some potential suggestions for how we may work forward from where we are.

TOP

So, the purpose of the SPORE grant, I think, is to identify new targets for either diagnostic or therapeutic intervention, and then, once the targets are identified, develop new therapies for the targets, and then test the hypothesis in preclinical models, and develop early clinical trials to evaluate, first, the safety and toxicity, and then the efficacy of these new therapies, and this would be the phase II trial portion.

TOP

To date, the current SPORE trials, almost all of them, except for maybe one or two that were mentioned earlier, are in the phase I portion.

Some of them are designed as straight phase I trials, a few are designed as phase I/II trials. Because most of the therapies are novel and they have been previously unstudied, they need a phase I portion.

The studies include vaccine trials, gene therapy trials, novel small molecules, monoclonal antibodies, angiogenesis inhibitors, immunotherapies.

TOP

Then, besides single agent therapies, novel combinations, you heard about a docetaxel VEGF trap study that is under design at M.D. Anderson.

One of the things, with these SPORE trials, many of the therapies are homegrown. They are in-house trials, and getting the homegrown therapy either available and exported to other places, or enough made in the clinical grade that can be used in other places can be a difficult issue.

TOP

The trials are expensive. The SPORE funds don't have funding to cover the clinical trial portion of the trial.

They have funding for collaborative science for the trials, but you have got to go out there, once you have this great idea, and find someone to fund it.

Potentially this could be done through CTEP or pharmaceutical companies or private industry, private philanthropy.

Currently we have a SPORE trial open now that we are trying to get funded through a private fund. Another potential way to fund the trials would be to partner with other funded groups, such as the GOG.

TOP

We face a lot of regulatory issues. We have a gene therapy trial open that we had to get FDA approval, RAC approval. We have to hold the IND , which is a big issue in some of these SPORE trials.

If it is an in-house homegrown therapy, you have to be monitored in the place where the trial is being done, and then to export that trial to other institutions can be very difficult and adds even more cost.

TOP

So, the four sites are listed here, UAB, Fred Hutch, M.D. Anderson, Fox Chase and Harvard. One potential area would be to collaborate between just the SPORE sites, and I think this is something that we have been talking about since the SPOREs began, but have not yet successfully done with any of our trials, mainly because of the issues I have mentioned in the last few minutes.

Another potential would be to collaborate between the SPORE and the GOG.

TOP

In order to collaborate, though, we keep hearing about prioritization of trials.

This is a difficult thing because every SPORE thinks that theirs is the most important trial to get done, including I think mine is the most important to get done.

If we collaborate with each other, how do we decide whose goes first? It could be done by stratifying patients based on eligibility criteria.

A lot of these are targeted therapies. So, we are looking for patients that specifically have an activation of a pathway or a mutation in a gene, or an overexpression of VEGF or EGFR.

It could be that, if the groups worked together, this could be done by stratifying patients to whatever protocol they fit.

Then who is going to oversee the trials. If it is an IND held trial, who is going to be doing all the monitoring?

Also, when you get multiple sites involved, you run into the issue of being able to perform the correlative science along with the trial that is part of the SPORE when you are getting tissue from other places.

We talked about SOPs and making sure that tissue is handled correctly, and making sure that it gets to the right place, but you also have to have the funding to do that. We have talked a lot about timing of completion of trials, and then who pays for the trails.

TOP

I titled these last two slides. First, I had suggestions and then I had ideas, and then I put future directions and maybe solutions. I don't know what the right answer is.

One suggestion would be that, in the SPORE trials, if the SPOREs focused on completing only the phase I portion of a trial in an individual site, this is going to be the most difficult, the most highly monitored part of the trial.

When they move on to the phase II portion, either open it up to all the SPORE sites, or the GOG as a whole, and develop a priority list based on when the trials are ready, and how the eligibility works out, depending on what markers you are looking at and what pathways you are targeting.

When a phase I portion of a study is funded, whoever is funding it, talk to them about potentially funding the phase II portion with a bigger group being involved.

There are a lot of legal issues that come up with the funding, too, and who is getting paid and who has the intellectual property and all of these things that have to be addressed, not just for the phase I portion, but also for the phase II portion.

We have also talked a lot about considering novel endpoints, to abort trials early that have ineffective therapies. CA 125 has been mentioned, novel imaging techniques, possibly other surrogate markers.

TOP

This is a difficult thing. If these SPORE trials are supposed to be innovative new therapies, they would have to have some kind of priority in a multi-site setting, possibly open to patients with multiple prior therapies that aren't eligible for other GOG trials, unlimited priors, say.

Maybe some kind of committee involving both representatives from the SPORE sites and the GOG could review the studies and review priorities, and also help develop the studies.

Again, the groups are going to have to work closely with the trial sponsors from the outset, address the regulatory issues that come up.

I think this is just a really important thing, that we have to develop mechanisms to increase patient accrual.

As we have all these new agents to study, we need patients to participate in the trials to get them complete. I think that is all I have to say. Thank you.

TOP