Dr. Grochow: In terms of how we decided previously to go on a trial, traditionally in phase I in those dose finding trials, it was any patient with any solid tumors and some patients with solid tumors and hemologic malignancies would go into phase I.

Now the question is going to be is the eligibillity going to based on the patient having the target -- is there any point in using a drug like Gleevec in a patient who doesn't have that target, even in a phase I setting. Let me limit somewhat the patients who undergo phase I. It may make phase I trials take longer to do.

In phase II, those activity trials we talked about earlier, they're going to change too because the traditional phase II role was to see what Dr. Sausville showed you; tumor shrinkage. But many of the new agents may not cause tumor shrinkage and they're looking for tumor stabilization, the elimination of progression of the disease.

That's a fairly easy thing to show if you're looking at a bunch of completely identical mice with completely identical tumors of completely identical sizes and you can look at ten and twenty mice in a group, but in human beings, when you're dealing with tumors of very varied progression rates which are unpredictable and change over time, showing that you've stabilized a tumor in the short term is not a very easy thing to do.

When are you going to look at the endpoint? Typically, for a phase II trial previously you gave the treatment for four weeks or eight weeks and then you did another X-ray, CAT scan or MRI. If the tumor had shrunk, you said, 'Oh, that seems to be helping you, we'll continue.' And that was a positive affect in terms of moving an agent along.

But with the new model, we're looking at tumor stabilization. Maybe we'll be looking at establishing functional -- and we don't know when those should even be looked at. There's some evidence, in terms of Gleevec, that within days of starting treatment you can see changes in the metabolic profile of extensive tumors. You may be able to look a lot sooner, but there are other agents where it may take a long period of time before you'd want to do that testing. We don't know when those research X-rays even should be done yet.