Barvarian Nordic provides update on randomized Phase III trial of Prostvac VF


According to a media release issued earlier today by Barvarian Nordic, the company expects to complete enrollment of patients in the randomized, double-blind, placebo-controlled, multi-center, Phase III PROSPECT trial of Prostvac VF within the next 12 months.

The full text of the media release also states that the total enrollment in this three-arm pivotal trial is 1,200 patients; that patients are currently being enrolled at nearly 100 clinical sites in 10 different countries; and that the company has reached an agreement with the U.S. Food & Drug Administration regarding planned interim analyses of the data (which might allow for the trial to be stopped early if there is clear evidence of superior efficacy in one of the three arms of the trial).

It also appears that Barvarian Nordic is hoping to be able to present information about a new trial of Prostvac VF in combination with enzalutamide at the upcoming annual meeting of the American Society for Clinical Oncology.

Prostvac VF is an immunotherapeutic agent (a “vaccine”) being tested in the treatment of men with metastatic, castration-resistant, chemotherapy-naive prostate cancer. Unlike the approved dendritic cell agent sipuleucel-T (Provenge), Prostvac VF is an “off-the-shelf” form of immunotherapeutic agent that does not require each dose to be individually created for each patient. Additional information about this trial for those patients who might be interested in exploring their eleigibility to participate is available on the Clinical Trials.gov web site and also on the Prospect trial web site.

12 Responses

  1. I am just starting this trial at the Marsden in the UK. As it is one third placebo I may have nothing to report, but if I do get the Prostvac drug will comment as I go along and if anyone has any questions please let me know

  2. Dear Robin:

    Isn’t this is a double-blind, randomized trial? I thought it was, in which case I don’t think you (or your doctors) are actually going to know which of the three treatment arms you are in until the trials is done.

  3. Yes you are quite right. However, after my first set of injections I woke up at night with a pain in my groin. My first thought was I would be dead in the morning but in the morning, when I was still alive, I saw one of the side effects of the drug could have caused the pain, so I am hoping I am not on the placebo, I am not clear, even at the end of the trial, just what I am told.

  4. Hi Robin.

    It is pretty much standard practice at the end of a trial like this to tell all patients still participating what arm of the trial they were in. The reason is that it is also pretty much standard practice to let all responders to stay on the product they were given and to tell patients in the placebo arm that they can be switched to the active product (if there is shown to be an active product that has a clear benefit compared to the placebo). So patients need to be told what they were receiving in order to make those decisions.

    By contrast, if you drop out of the trial early for any reason, you will almost certainly not be told which arm of the trial you were in because (cumulatively) that information could prejudice the trial blinding.

  5. One year on — any news? I have just started having had the second injection 2 days ago. It is impossible (for me, anyway) to determine which “arm” I am on but, hopefully, if I am on the placebo “arm” I will be able to last the course.

    Graham

  6. Dear Graham:

    This Phase III trial enrolled its last participant on December 10, 2014, so you must have been one of the last men to be enrolled.

    The currently estimated completion data for the study is December 2015, which suggests that we might be able to hear the preliminary results of this trial at the Genitourinary Cancers Symposium in San Francisco in about February 2016.

  7. I wonder if I might be permitted to question the aetiology of this trial, and also to clear up some facts.

    I have read that the purpose of the trial is (1) to confirm there are no unpleasant side-effects and (2) to determine life-expectancy improvements arising from treatment with the vaccine. I believe (1) to be straightforward: with 1200 participants it should not prove difficult to find out if any patients have had serious side-effects. It is with (2) that I have a problem.

    Improved life-expectancy can only be determined if, from the moment the patient starts the trial to his death, he remains solely on PROSTVAC or placebo. This is patently obviously not going to happen. If a patient has the misfortune to be chosen for the “dummy/dummy” arm it will soon become apparent he is getting no benefit and will ask for an alternative (enzalutamide, abiraterone, chemotherapy, etc.) which must negate the forecasting of his life-expectancy as a “dummy/dummy”. Even those patients on the live vaccine arm will doubtless eventually take a different drug. As we are all different, these different drugs are bound to affect patients differently. This will seriously confuse the life-expectancy calculations due to PROSTVAC alone.

    Finally, a personal question: if I find I am on the placebo does the trial protocol then offer me the live vaccine at the end of the trial?

    Graham

  8. Dear Graham:

    All clinical trials of all drugs used to to treat late stage disease face the issue you describe under your item (2).

    You need to appreciate that the way all such trials are designed is therefore, almost always, to measure the differences in overall and/or disease-specific survival between the arms of the trial regardless of what other forms of therapy patients may be given after they have received the specified treatment. (In the case of the Prostvac trial there are actually three arms to the trial). And so all patients are followed until death regardless of whether they have other treatment. However, it is customary to keep careful records of what those other treatments have been so as to see if the differences may be having other effects on survival that can be assessed and analyzed.

    Does this complicate the interpretation of the results of these trials? Sure it does, but the medical and pharmaceutical communities (and their specialized statisticians) have many years of experience in knowing how to sort the wheat from the chaff in understanding the results of such trials. It is my opinion that Prostvac will have to show a very distinct overall survival benefit in one or other or both of the two “active” arms of this trial (compared to the “dummy/dummy” arm) if it is going to be clear that it is offering a real life extension benefit.

    With regard to your item (1), let me just be clear that it is not the goal of the trial to “confirm that there are no unpleasant side effects”. Almost all drugs can have unpleasant side effects in some people. The goal of the trial is rather to understand the risks for such side effects so that we can avoid giving the drug to patients for whom the risks would clearly outweigh the benefits and to be aware of the level of other, manageable risks.

    With respect to your final, personal question, it is customary for patients in trials like this to be offered the active drug at the end of a trial if the drug shows a significant benefit compared to the placebo or other treatment arm. So it is probably impossible to know, at this time, whether Barvarian Nordic will be able to make such an offer to the patients who are on the placebo-inclusive arms of the trial. The company will only know this when they actually have the trail results, because whether they make this offer will undoubtedly depend on whether there really is a clear and significant survival benefit.

  9. This gives rise to yet another query!

    If, as you say, it is customary to offer patients who have been on placebo the active medication, then how is it possible to determine improvement in life expectancy. If I have read you correctly, eventually all participants will receive the PROSTVAC.

  10. Graham:

    No one who receives the placebo gets the active product (Prostvac in this case) until after the trial endpoint has been met. Thus the trial result is known before anyone receiving the placebo is offered the active product.

  11. Please forgive me if you think I am deliberately trying to be objectionable. I am sure you will understand that as a participant in a drug trial that could make a significant difference to my life I am trying to get MY facts straight, i.e., to understand the situation better.

    If the aim is to see whether there is any change in life expectancy then this can only be achieved when (sadly) a goodly number of people have died — from all three arms. Hopefully, this may be many years hence: in which case the “placebo arm candidates” will be denied access to the active drug for a very long time?

  12. Dear Graham:

    As I mentioned in a reply to one of your prior questions, the currently estimated completion data for the study is December 2015, which suggests that we might be able to hear the preliminary results of this trial at the Genitourinary Cancers Symposium in San Francisco in about February 2016. You need to remember that the first patients started to be enrolled into this trial quite some time ago.

    You also need to appreciate that this is the way that clinical trials have to work, because the bottom line is that a new experimental agent may have little to no effect on the long-term survival of patients compared to a placebo. If it does have a significant effect, that will become apparent quite quickly. If it doesn’t, that will still become apparent quite quickly. Men with castration-resistant, metastatic prostate cancer don’t exactly have a long life expectancy on average.

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