Those of us with challenging cases have been paying close attention to the clinical trial and FDA approval process for Provenge, an immune system drug that should be approved by the FDA sometime next year. (I'm basing that last statement on the fact that the developer, Dendreon Corp., negotiated what amounted to a contract with the FDA that the drug would be approved if the results in a key 512 patient trial achieved a pre-specified level of success. Last spring Dendreon announced that the trial had reached the required success level. Dendreon's application for approval was acknowledged as complete by the FDA per a Dendreon news release on November 20.) If interested, you can find 29 previous posts about Provenge by using the board's index.
The FDA now has an official deadline (known by the industry nickname as the "PDUFA date") of May 1, 2010 to announce whether Provenge is approved. Hopefully, approval will be more rapid, but it could also be slower. (Based on the very strong evidence of effectiveness for some men, there is high confidence the drug will be approved at some point in the near future.)
Meanwhile - here's the great news - Dendreon has been moving to make Provenge available prior to approval for that group of patients covered in the application to the FDA, and, since 9/18/2009, such men are being recruited for the "trial"!
Essentially, that group includes men with hormone refractory prostate cancer (meaning that hormonal therapy can no longer control the cancer) who have metastases. Note that the trial rules were changed on 9/18/2009 to expand trial eligibility that had previously been restricted just to men who had been in the placebo group for previous Provenge trials.
A group I belong to heard a speaker from Dendreon yesterday and we had ample opportunity to ask questions and interact in a two hour session.
He told us that Dendreon had set up a clinical trial that will enable access to many patients who could benefit from Provenge now, prior to FDA approval. In effect, this is a compassionate use program. The trial is officially designated (Government designation: NCT00901342) as "P09-1 (Open-Label Active Cellular ImmunoTherapy) - Title: An Open-Label Study Of Sipuleucel-T [the official name for the key element in the drug]
In Men With Metastatic Castrate Resistant Prostate Cancer." ["Castrate Resistant" is virtually the same as "hormone resistant, meaning that the cancer is progressing despite having a patient on hormonal therapy who has achieved a very low ("castrate") level of testosterone, which shows that the hormonal therapy is doing what it was designed to do; in other words, hormonal therapy is no longer able to control the cancer.]
(Now back to black type - still my words, but not as a comment on the official designation of the trial.)
The "trial" is what is known technically as a single arm (meaning no control arm, therefore no placebo - Dendreon already succeeded at that), open-label (meaning both the patient and doctor know what the patient is getting - no double or single "blinding" since they also already succeeded at that). Here's what the company said about the trial, with some of my comments in green: "Study Design and Duration: Potential subjects with metastatic CRPC will undergo screening procedures to ensure they meet the inclusion and exclusion criteria outlined in the protocol ["protocol" means the rules of the trial]
. If eligible, subjects will undergo a standard 1.5 to 2.0 blood volume leukapheresis ["leukapheresis" means that blood is drawn out of the patient, and in this case, it will be processed with the drug and then returned to the patient]
, followed 3 days later by an infusion of sipuleucel-T. This process will be repeated at approximately 2 week intervals for a total of 3 infusions [3 is the planned number of infusions once the drug is approved]
. Study duration is approximately 60 days and includes two follow up office visits within the first month of the last infusion. D9902B subjects who received placebo can participate in this study." What all this means is that patients in the trial will get the same Provenge in the same way as patients will get it once the drug is approved by the FDA.
Okay, so the rub in such trials and compassionate access programs is often the eligibility requirements
, and we've already had at least one post on the board about a patient who was ineligible for earlier access, I believe because he lived too far from a trial site to satisfy a mileage restriction. My impression is that Dendreon has gone a long way toward making the drug available in a practical way that will actually work for many patients. Among other things, Dendreon has already set up nine trial sites and is working on more; my group is from Virginia, and we learned there was one site in Virginia and were two in Maryland. Earlier trial requirements included a PSA of at least 5; now, per official deletion of that requirement on 11/24/2009, that is not a requirement if there is imaging evidence of progression. Earlier there was a mileage restriction - the patient had to live within so many miles of a trial site. Now that is not the case. AND, the cost is zero to the patient, according to the speaker, at least for the drug cost!
Here is an excerpt from the eligibility requirements listed at www.clinicaltrials.gov , a site we can use on this board because it is Government sponsored. I'll put the official requirements in blue and comment in green: ...
For a subject to be eligible for participation in this study, all of the following criteria must be satisfied.
Castrate resistant prostate cancer.
Castrate level of testosterone (< 50 ng/dL) achieved via medical or surgical castration. The experts in hormonal therapy that I follow all think that level - <50 - is too high. They believe that you should not really count a patient as resistant to hormonal therapy until he cannot achieve a testosterone level <20. Many times they have found that a patient will still respond to hormonal therapy by making changes in the drug regimen. Still, if a patient meets the stated criterion of disease progression despite a testosterone level of <50, he would satisfy this criterion.
Life expectancy of at least 3 months.
Adequate hematologic, renal and liver function.
A subject will not be eligible for participation in this study if any of the following criteria apply.
The presence of known lung, liver, or brain metastases. [This requirement eliminated a friend of mine from eligibility.]
Evidence of neuroendocrine or small cell features. [These features are truly rare. They indicate an extremely aggressive and hard to treat kind of prostate cancer. It's possible that Dendreon has already learned that Provenge will not help such patients, but I do not know that - just somewhat informed speculation.]
Eastern Cooperative Oncology Group (ECOG) performance status > 2. [That ECOG status means that the patient more than this much impaired: "Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours." This requirement would rule out patients in Status 3 - 5, who are worse off: "[Status] 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
[Status] 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
[Status] 5 Dead [Yup, makes good sense: hard to have a stiff participate in a trial, unless his name is Bernie - please excuse a little black humor.
Prior treatment with 3 infusions of sipuleucel-T (infusions of APC8015F are not exclusionary)
Imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression.
Known malignancies other than prostate cancer that are likely to require treatment within six months of registration.
A requirement for systemic immunosuppressive therapy for any reason.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF [This restriction would rule out men with an allergic reaction to Leukine. I assume the kind of allergic reaction would be more than just a routine and minor injection site reaction, but I'm not sure.].
Any infection requiring parenteral antibiotic therapy or causing fever (temp > 100.5F or > 38.1C) within 1 week prior to registration.
Any medical intervention or other condition which, in the opinion of the Principal Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.
Treatment with any of the following medications or interventions within 28 days of registration:
Systemic corticosteroids. Use of inhaled, intranasal, intra-articular, and topical steroids is acceptable, as is a short course (ie, ≤ 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans.
Non-steroidal anti-androgens (eg, bicalutamide, flutamide, or nilutamide). [I would hope and expect that men being considered hormone refractory would at least have been on one of these drugs at some point. But a gap of at least 29 days will make the patient eligible.]
External beam radiation therapy or major surgery requiring general anesthetic.
Any other systemic therapy for prostate cancer including secondary hormonal therapies, such as megestrol acetate (Megace®), diethylstilbestrol (DES), and ketoconazole. Same comment as for the antiandrogens.] Medical castration therapy is not exclusionary.
Treatment with any other investigational product.
It's worth noting that there is no PSA level restriction nor any mileage restriction.
Here are the doctors leading the trial at each of the official sites (eight are listed below - including seven published by Dendreon and one additional site on the official US Government website www. clinicaltrials.gov - in alphabetical order by state. Apparently one more has been finalized but is not yet listed). Dendreon has published more details on who to contact with phone numbers and email in addition to what is included here. Here's the list:
Chadi Nabhan, M.D. - Oncology Specialists, S.C., Chicago, IL
Georgetown University Medical Center Recruiting
Washington, District of Columbia, Nancy Dawson, MD
Myron I. Murdock, M.D., LLC, Baltimore, MD
Daniel Petrylak, M.D. - Columbia University Medical Center, New York, NY
Simon Hall, M.D. - Mount Sinai School of Medicine, New York, NY
Andrew Armstrong, M.D. - GU Oncology Research Program, Durham, NC
Raymond Lance, M.D. - Urology of Virginia / Sentara, Norfolk, VA
John Corman, M.D. - Virginia Mason Medical Center, Seattle, WA
You may be wondering what the company gains from this trial, considering that they already have the data they need for FDA approval. Here are the purposes Dendreon has published: "To provide sipuleucel-T to men with metastatic CRPC while marketing approval is being pursued, obtain safety data, evaluate the magnitude of immune responses to treatment with sipuleucel-T, and to further characterize the cellular components of sipuleucel-T." All four objectives are credible to me. They will learn more about the drug and how to use it, but they will also be able to reach out compassionately to patients in need. I believe they are sincere in that, and, on behalf of fellow survivors and their loved ones, I'm grateful. Unfortunately, I had a friend Andy who dearly wanted access to Provenge, but he passed on several months ago.