I've found something quite unusual, and would like someone to confirm the unusual dynamics, as I am on unfamiliar turf. Apparently, an older & fully recruited EXEL-sponsored trial has been expanded w/in the jurisdiction of the MD Anderson Cancer Center (though not limited to MDACC - or so it would appear). No IST has been designated for this patient accrual, and the numbers appear relatively large.
Here are the #'s. NCT00215605 solid tumors - fully enrolled & no longer recruiting having a proposed enlistment of 77 patients by the trial listing at clinicaltrialsdotgov.
And - at the MD anderson site: clinical trial 2005-0396SOLIDTUMORS. Per the website, no longer recruiting...but a recent (July 2012) IRB places accrual at 500 (!!!) patients. This trial lists NCT00215605 as the federally listed reference trial for study guidelines, and would appear to be the original source of the MDACC study.
The published purpose of the MDACC study:
"The goal of this study is to allow you to continue to receive cabozantinib for
as long as your study doctor thinks you are benefitting from it, even if your
previous study or study arm has already closed. The safety of cabozantinib and
its ability to control advanced disease will also be studied."
This would appear to be some sort of unofficial expanded access, thereby guaranteeing clinical access to Cabo as long as patient benefit warrants. Am I reading this wrong? Ernie, do you have a take on this? Anyone?
NCT00215605. I think Doc has it right. It is an Exelixis sponsored extension study to continue treating patients from any of the discontinued studies, which is why the estimated recruitment does not match. Legally, EXEL needs an IND to under which to prescribe the drug and I guess it is easier to recycle the phase one protocol than to apply for a new one.
There is not really any other logical explanation, and it is a very good sign, at least for me. I keep saying, this company is on to a huge winner.IMO Anybody who does their own DD will find it hard to dispute either the probable expanded use or the efficacy possibilities. No way they would continue, or expand any study if things were not looking good. How good? Now I think that could be a rocking good!
this has all the appearances of an "extension" trial. What happens is that patients are treated for a proscribed time on a specific trial. At some point, for administrative purposes, it is desirable for a sponsor to close a study (e.g. to submit final documents, to lock a data base for unblinding, etc.). In this case, if patients have been followed enough on one study, haven't progressed, but the sponsor needs to close the study, these types of studies are one mechanism to continue to make drug available to patients (clearly the appropriate and ethical thing to do). Note that one inclusion criteria for the solid tumor trial is prior enrollment on an XL-184 trial. This also allows patients to continue to have data collected to provide possible longer term safety data which might be helpful to Exelixis.
In my experience, this is pretty routine, the alternative being to wait until the final patient is off study before closing the study down.
The accrual #'s threw me a'wonderin' whassup. With an indicated initial enrollment of 77, how would we arrive at a more recent IRB annotation of 500...? I understand the ethics of enabling access to those who benefit...but where in the heck would the other 400 patients have come from...?? It would appear there may be a lot of patients receiving benefit from Cabo that may be unaccounted for...
....and that's a good thing for patients. But someboby might wanna tell the shareholders that we've got an additional 400 patients on the prescription roster that might be realizing some measure of advanced benefit & we'll let you know someday...
It just seems like a pretty cavalier, devil-may-care method of clinical accounting...
Oh...by the way - we have these 400 patients over here we've been monitoring for the past 6 years that're doing quite well...and stand to outlive Methuselah if we keep them on the Cabo program.
Where's the transparency? By the clinical mandate, the trial is done...isn't it?