Texas Vaccine Trials Opening up

[Janelle]

Two vaccine trials are opening up in Texas for early stage Her2 patients. You must currently be NED, at high risk for recurrence and within 6 months of your last active treatment (including herceptin) to enroll. (At least that is my understanding.) The trial at MD Anderson is a phase 2 trial of a single peptide (I think)....You may be randomized to a non-vaccine arm if you enroll in the MD Anderson trial.

The trial that is opening at the Mary Crowley Cancer Center in Dallas is a phase 1 trial and involves multiple peptides for the vaccine. Since it is a phase 1 trial they are studying safety among other things so you may not receive what will prove to be the optimal dose of the vaccine. You will get some of the vaccine in any case.

If you are interested in these trials, please contact either Dr. Mittendorf (if you want more info on the MD Anderson trial) or Neil Senzer if you are interested in the Mary Crowly phase I trial. I am in no position to vouch for the accuracy of the statements in this email as I am summarizing my understanding of each trial but I am not an expert.

The below email is from Dr. Elizabeth Mittendorf at MD Anderson:

"It appears that the phase 1 trial looking at the multiepitope vaccine will launch at the Mary Crowley cancer center at the end of this month or early Aug. The point of contact is as follows:

POC Neil Senzer… nsenzer@marycrowley.org

We are anticipating that we will launch the phase II trial here at MDACC around the same time.

Please keep me posted as to how you would like to proceed and let me know if I can provide you with additional information. "

Beth

Elizabeth A. Mittendorf, M.D.
Assistant Professor
Department of Surgical Oncology
U. T. M.D. Anderson Cancer Center
1515 Holcombe Blvd. Unit 444
Houston, TX 77030
eamitten@mdanderson.org

[Janelle]

Below is the email that I sent to Dr. Mittendorf with more questions. I'll post her response when I recieve it.


"Dr. Mittendorf,
To clarify (and beat a dead horse)....the phase 2 trial at MD Anderson requires that 50% of the enrollees will be randomized to a GM only arm which is possibly similar to a placebo arm, correct? And it is the phase II of the E75 trial that is being started?

Are you still the point of contact for the MD Anderson trial?

I have more questions about the history of the phase II trial. Should I contact a POC other than you to get these answers? Here are my questions:

I noticed through some research that one person who enrolled in what I believe to be the was phase I HER2 vaccine trial trial had to discontinue the trial due to cardiac toxicity. I am not sure if she was enrolled in phase I of the E75 trial or a trial at another institution for metastatic patients. Do you know of any people experienced cardiotoxicity in the phase I trial of the E75 vaccine or any other vaccine trials? If so, were these patients heavily pretreated with cardiotoxic chemo (specifically with A/C chemo) or targeted therapies prior to enrollment? And, did their heart function improve once they discontinued the trial? I assume all the enrollees had normal heart function results to qualify for the phase I study but please let me know if this assumption may be incorrect.

What was the average age of the phase I participants? Do you think age was a factor in any cardioctoxicity if any patients who had to discontinue the respective vaccine trial due to this complication? (Knock on wood, but as far as I know, my heart function is good (high normal).) I am also under 40 which may or may not help me tolerate the drugs....and I was a jogger for 15 years prior to diagnosis.

To the best of your knowledge, are you aware of any enrollees in HER2 vaccine trials had to drop out due to significant adverse events other than cardiotoxicty, what were those events? Did they recover?

Since the phase 1 trial at Mary Crowley is in part studying the safety of the multipeptide vaccine as you pointed out and I will be an early enrollee I am trying to determine if the other vaccine trials are a reasonable basis for comparison as I attempt to assess the risks that I will take by enrolling in this trial. Or do you feel that the other vaccine trials are not good for safety comparisons for other reasons? If so, what are those reasons?

I understand and acknowledge that the phase 1 trial is designed to test the safety of the drug and you may be unable to give me any reassurance on the safety issues. But if you can give me any guidance as to how I should proceed to think about these safety issues that would be helpful. Otherwise, can you recommend a way for me to do a comparison myself or is the date not available to the public yet on the other vaccine trials?

My very conservative oncologist did not seem to be overly concerned about the safety issues with either trial the MD Anderson trial or the Mary Crowley trial based on the information that I gave her which reassured me. But I am very analytical by nature so I am interested in as much information as is available to me. I will ask Neil for more information on the phase I trial unless you are the better person for me to get such information. Feel free to pass this email along to Neil. I am not copying him on this email as many of my questions involve the MD Anderson trial in which he may have involvement.

If I chose to enroll in the MD Anderson trial, how long will the trial last? Will I need to travel to Houston every month for 6 months? Or are the vaccines administered over a more compressed time period? How long will I be required to stay in Houston for each vaccine administration?

I would like any updated information on both trials that you have not already provided to me so I may review the most recent information again with my oncologist.

By the way, one more question which is off topic....Has MD Anderson started giving Zometa to early stage breast cancer patients to prevent bone mets or do you think they will begin to do so? I understand if you can't answer this question as I am not a patient at MD Anderson but I am asking in terms of generalities and not seeking information specific to my own treatment plan."

Thanks again!
Janelle

[dhealey]

Janelle, I believe this is the same Phase II trial I wil be starting next week at Wake Forrest here in North Carolina. From the info I was given, no one here suffered any cardiac problems or had to drop out in the Phase I trial conducted at Wake. My understanding is that there will be no placebo arm in the trial I am participating in. I am meeting them at Wake on Tuesday for one more blood test and sign a consent form. I will start the vaccine the following week. I was told they have 9 testing site across the country for this trial. You must be no more than 6 months out of treatment. I almost did not get in as I am at that six month point. I will let you all know more as I move along in the trial.

[Janelle]

Debbie,
Wow, I would be really interested if in the Wake trial if no randomization is involved (or the same trial at a different location). How many times will you get a vaccine and over how many months? Thanks for the info!

Janelle

[Janelle]

Here is the response that I received from the doctor at MD Anderson regarding my questions about the vaccine trials:

With respect to your questions:

To clarify (and beat a dead horse)....the phase 2 trial at MD Anderson requires that 50% of the enrollees will be randomized to a GM only arm which is possibly similar to a placebo arm, correct? And it is the phase II of the E75 trial that is being started? The phase 2 trial that is close to starting at MDACC will randomize 50% of patients to GM alone, that is correct. It is also fairly accurate to compare GM alone to a placebo since those patients are not being administered the peptide which is what we believe stimulates the immune response.

This phase II trial is for GP2 (the cousin of E75 that also stimulates CD8 cells) and AE37 (a HER2 peptide that stimulates CD4 cells). It is a 4 arm trial, HLA-A2+/A3+ patients randomized to either GP2+GM or GM alone and HLA-A2-/A3- patients randomized to AE37+GM or GM alone. Your HLA status is just one of your genetic characteristics; as an example, approx 50% of the population is A2+, about 15% of the population is A3+.

The phase II trials for E75 have already been completed and published in Cancer Research this past Feb. The next trial for E75 will be a phse III trial, likely run by a company called apthera which has licensed the peptide.

Are you still the point of contact for the MD Anderson trial? Yes

I have more questions about the history of the phase II trial. Should I contact a POC other than you to get these answers? Here are my questions:

I noticed through some research that one person who enrolled in what I believe to be the was phase I HER2 vaccine trial trial had to discontinue the trial due to cardiac toxicity. I am not sure if she was enrolled in phase I of the E75 trial or a trial at another institution for metastatic patients. Do you know of any people experienced cardiotoxicity in the phase I trial of the E75 vaccine or any other vaccine trials? If so, were these patients heavily pretreated with cardiotoxic chemo (specifically with A/C chemo) or targeted therapies prior to enrollment? And, did their heart function improve once they discontinued the trial? I assume all the enrollees had normal heart function results to qualify for the phase I study but please let me know if this assumption may be incorrect. We have had no patient on the phase I or II E75 trial experience cardiac toxicity. In fact, no patient withdrew from the trials due to any toxicity. One point that I would emphasize (and will do so again below) is that the vaccines so far have been found to be very safe. Less then 20% of patients even experience mild systemic toxicity (ie grade 2). As a caveat, our trials to date have not mandated patients to have MUGA scans to assess cardiotoxicity so there is the remote possibility that patients have experienced a subclinical toxicity. Moving forward into our combination immunotherapy trials when we combine herceptin with the vaccine, we will be assessing ejection fractions as part of the protocols. Since you have ocmpleted herceptin, you would not be eligible for that phase I trial.

What was the average age of the phase I participants? Do you think age was a factor in any cardioctoxicity if any patients who had to discontinue the respective vaccine trial due to this complication? (Knock on wood, but as far as I know, my heart function is good (high normal).) I am also under 40 which may or may not help me tolerate the drugs....and I was a jogger for 15 years prior to diagnosis. Ave age for the E75 trials was early 50s. I hope when you say "was a jogger", you don't mean you've given up running. I find that running (I'm one of those crazy types who enjoys running marathons) is very good for my mental health!

To the best of your knowledge, are you aware of any enrollees in HER2 vaccine trials had to drop out due to significant adverse events other than cardiotoxicty, what were those events? Did they recover? As above, no patients have dropped out of our trials due to toxicity.

Since the phase 1 trial at Mary Crowley is in part studying the safety of the multipeptide vaccine as you pointed out and I will be an early enrollee I am trying to determine if the other vaccine trials are a reasonable basis for comparison as I attempt to assess the risks that I will take by enrolling in this trial. Or do you feel that the other vaccine trials are not good for safety comparisons for other reasons? If so, what are those reasons? I'm not sure exactly how best to answer this question. I think it would be good to point out that a multiepitope vaccine isn't really mixing the peptides together. What effectively is going to happen is that patients will be administered 2 vaccines; the GP2 vaccine AND the AE37 vaccine. Each of these stimulates a different arm of the immune system (see above). The amount of GM-CSF, which arguably is the agent causing the toxicity that we see (albeit minimal txocitiy) is held constant. The doses for each peptide in the initial steps of this phase I trial are very low. We fully expect that we will be able to progress to our highest proposed dose groups without serious toxicity but again, as you point out, that is the reason to do a phase I trial.

As an aside, what we are anticipating is that administereing both peptides will stimulate both arms of the immune system resulting in synergy i.e. a more robust and more sustained imune response.

I understand and acknowledge that the phase 1 trial is designed to test the safety of the drug and you may be unable to give me any reassurance on the safety issues. But if you can give me any guidance as to how I should proceed to think about these safety issues that would be helpful. Otherwise, can you recommend a way for me to do a comparison myself or is the date not available to the public yet on the other vaccine trials? see above

My very conservative oncologist did not seem to be overly concerned about the safety issues with either trial the MD Anderson trial or the Mary Crowley trial based on the information that I gave her which reassured me. But I am very analytical by nature so I am interested in as much information as is available to me. I will ask Neil for more information on the phase I trial unless you are the better person for me to get such information. Feel free to pass this email along to Neil. I am not copying him on this email as many of my questions involve the MD Anderson trial in which he may have involvement.

If I chose to enroll in the MD Anderson trial, how long will the trial last? Will I need to travel to Houston every month for 6 months? Or are the vaccines administered over a more compressed time period? How long will I be required to stay in Houston for each vaccine administration? if you enrolled in the phase II trial at MDACC, you would need to travel to Houston basically once per month for 6 months and plan in staying in town approximately 2-3 days each time. After administration of the vaccine, you need to be seen 48 hours later to assess for local toxicity at the injection site.

I would like any updated information on both trials that you have not already provided to me so I may review the most recent information again with my oncologist. I hope the responses above give you the desired information.