Good afternoon. For those of you who don't know me, I work in the Investigational Drug Branch. Dr. Michaele Christian is my boss. Dr. Ted Trimble is my colleague.

Ted gave me the task to present to you today an overview of the productivity of CTEP-sponsored phase II trials in ovarian cancer.

This is a little bit different from what I am usually asked to talk about, which is an overview of the scope of the program related to the number and types of agents, the types of trials in the portfolio.

Instead, what I am going to focus on is just to give you an overview about the number of requests we receive, the number of LOIs we receive, the number of requests or solicitations that we sent out, how many trials we approve on an annual basis, and the track record for protocol development and patient accrual.

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What I did, to put together this presentation for you, was to go through the CTEP database of clinical trials between 2000 and 2005, and look specifically at phase II trials, or phase I/II trials, of investigational agents where CTEP holds the IND, and these trials are specific for epithelial ovarian carcinoma. So, in that period of time, between 2000 and 2005, we received 100 LOIs. Of those 100, 36 were approved.

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In addition, in the last three years, we have sent out 14 solicitations for high priority investigational agents that included requests for proposals for phase II trials, and half of these solicitations included requests for phase II trials, either single agent trials or combination trials, in ovarian carcinoma.

On this slide, I have listed the spectrum of agents that were covered in these solicitations and, as you can see, they are heavily weighted toward novel targeted agents.

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In total, we are currently evaluating 22 different agents. Again, they cover the spectrum of targeted agents, immunotherapy, biological agents, and cytotoxic agents.

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In terms of the number of approved LOIs, the institutions or groups that have received approval of their proposals are fairly evenly divided between center institutional studies, consortia, or multi-institutional collaborative studies, and the GOG.

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In terms of the number of trials that we approved over the last five years per year, we approved a median of six trials with a range of two to nine in each of the last five years.

So, clearly, the scope of the program that is supported through CTEP sponsorship, through its IND program, is considerable.

In terms of the number of trials that are currently active and accruing patients today, involving CTEP-sponsored IND agents, there are 21 actively accruing trials.

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Reviewing clinicaltrials.gov to give you some comparison with non-industry trials, we identified 25 phase II early clinical trials involving investigational agents in epithelial ovarian cancer.

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However, there are issues that have been raised previously with the number of trials, the timeliness of the completion of those trials, such that we have answers that we can subsequently move on to additional development, either with the agent itself in epithelial ovarian cancer, or turning to other agents that look more promising.

TOP

When we look from the time of LOI approval to receipt of the protocol, we can see that, in some respect, cancer centers are perhaps more adroit.

They can usually turn around a protocol in a median of about two months. The groups are somewhat slower, no doubt reflecting the more complicated protocol writing and approval processes that they have internally.

If we look at the time from LOI approval to protocol activation, this would be the time either the protocol is ready to be activated at sites in group studies or whether, for cancer center studies, activation actually means the first patient has been enrolled.

Again, we can see that cancer centers are somewhat better in getting the trials open, activated and accruing patients than perhaps some of the other sites are, or other groups are.

If we look at the rates of accrual per month to these early clinical trials, it is quite clear that the groups do better, and that is not surprising, with the cancer centers having a median of less than one patient accrual per month, and the groups doing somewhat better, and particularly the GOG, to its early clinical trials with evolving investigational agents being around two patients per month.

Clearly, this is not a considerably large number of patients who are being accrued across this rather diverse and large program.

TOP

The net result is, of course, that the duration from LOI approval to closure of accrual is quite long. The minimum of the trials that have been completed in that five-year period, from 2000 to 2005, the minimum interval between LOI approval to closure to accrual was 26 months, and that was the GOG study.

TOP

For the trials approved between 2000 and 2005 that have completed accrual to date, I can say that approximately three or more years, perhaps considerably more than three years, may be required to complete accrual for these studies.

TOP

This is, of course, a database analysis. So, there are some limitations I want to point out. The milestone dates on which I presented the data to you has been reported and entered into the CTEP database, and I haven't confirmed these dates and numbers with the sites at this point in time.

The accrual per month is the average over the duration of the study activation to the closure of accrual. So, studies that have a hiatus between the first stage and the second stage would, of course, in that monthly accrual, actually have a somewhat decrease in the monthly accrual rate, reflecting a period of time when the studies actually temporarily closed to accrual.

TOP

Nonetheless, these data do raise a number of issues, which I am sure you are all familiar with. Many of these issues have been touched on already by Dr. Spriggs. Many of them were raised this morning. I simply provide to you some numbers around the issues that were raised.

There are clearly delays in the development of protocols, and we would be curious to know what these might be, and how they might be addressed.

There are clearly delays in protocol approvals and activation, and there are significant delays in the accrual rates, leading to conclusion of the study and the reporting of results.

I look forward to the discussion around the points raised initially by Dr. Spriggs in order to address this, so that we can more efficiently evaluate important agents and develop new therapies for patients with epithelial ovarian cancer. Thank you very much.

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