Interview with Dr. McCormack

Dr. McCormack Answers Questions from LAM Patients Regarding the MILES Trial

When did the trial open and what future MILES Trial sites are planned?

The first patient was enrolled at Cincinnati Children's Hospital in late December 2006. Other sites will include the NIH in Bethesda, MD, Charleston, SC, Tyler, TX, Gainesville, FL, Cleveland, OH, Portland, OR, Denver, CO, Osaka/Niigata, Japan, Boston, MA, and UCLA, CA.

Please give a brief review of the timeline for the MILES Trial, once it gets started.

We anticipate it will take two-three years to enroll all patients. There are six visits in the first year, and two in the second year. There will be an interim analysis when 50 patients reach the 1-year point. The trial will take 3 years to complete.

What are the risks and/or side effects of the drug?

The predictable risks are mouth ulcers and cholesterol problems, which affect about half the patients that take the drug. These are almost always self-limited and manageable. The bigger worries are infection and a pneumonia-like syndrome, but they are much less common.

What costs are involved in a trial?

Patients pay nothing for the drug or trial visits. Travel expenses are funded for all US participants. LAM patients outside the US who wish to participate in the trial may call Sally Lamb at the Foundation for more information. Insurance is used to pay for unexpected problems (bronchitis, etc.).

Has a LAM patient been taken off of a transplant list because this drug improved functions and shrinkage in blockages or is it still too early to tell?

It's too early to tell. No one should enroll in this trial instead of being listed for transplant. Our hope is that this will be an effective treatment, but that needs to be proven.

When a patient enrolls, does she have to stay in the country (where the trial is) for at least 1-2 years?

Patients need to return for a total of eight visits over two years, but do not need to stay in the country in-between.

If sirolimus is proven effective as a drug to treat LAM, would it be possible to introduce it into countries that are not a trial site?

It will be available to patients in countries where the drug is available. Whether insurance will cover it is less clear. There are many countries, such as Japan, that do not import rapamycin, and many regulations govern this process. It is difficult but not impossible to obtain the drug under these circumstances.

What are the requirements to be in the trial? I will be completing chemotherapy for breast cancer in August. Can I still be considered?

I am sorry, no. We have excluded people who have had cancer within two years, because there is a theoretical risk that sirolimus could contribute to the spread or recurrence.

What is the purpose of the Trial? To prevent? To cure? To find a more efficient medicine than progesterone?

The purpose of the trial is to determine if sirolimus has a beneficial effect on lung function. Ultimately, we want to know if it improves survival and slows progression, but those answers will require other trials.

How much time will the trial take and when are results expected?

The trial will take three years, the earliest possible results will be in 1.5 years.

My disease is severe - would I still be considered for the trial?

Yes, there is no exclusion based on severity.

How often is the test done?

Trial visits involve lung function tests, CT scans and lab tests, but no invasive tests like bronchoscopy. They occur every three months the first year and then every six months the second year.

Can I still be in the trial if I'm on oxygen?

Yes.

What would happen if I get called for transplant during the trial?

You cannot be actively listed for transplant at the same time you are in the trial.

I had a single lung transplant and still have LAM in the other lung. I would like the opportunity to participate. I was put on sirolimus once after transplant but it got too expensive and I had to go off.

Previous lung transplant is an exclusion. I am sorry.

While on the trial, will we be given a recommended diet, exercise program and areas of possible trouble? Is it similar to chemotherapy precautions?

Yes, there will be information sheets about sirolimus, mouth ulcers, and cholesterol management.

Is the MILES Trial better than hormonal therapy?

Hormonal therapy is unproven. We are hopeful that the MILES Trial will prove whether or not sirolimus improves lung function in LAM. That is the purpose of the trial.

If some of the side effects (high cholesterol, fat in the blood, mouth ulcers) will tell for sure that you're on the drug, why use placebo?

You are correct that side effects will ‘unblind' the trial in some cases, that is, it will be clear to the doctor that his/her patient is on the active drug. But even an imperfect blind is better than no blind.

I know there are eight visits over a period of two years. Does each visit require a return trip to the enrollment center or can some of it be done through my doctors in my hometown?

All visits must be at a rare lung disease center (RLDC) site. Although we do not encourage it, it is possible to have some visits done at a different site than where the baseline visit was done. You must do baseline, 6, 12 and 24 month visits at the same center. The 3 week, 3 month, 9 month and 18 month visit can potentially be done at another RLDC site.

If I have had breast cancer in the distant past is it too much of a risk taking sirolimus?

At this point you are considered cured from breast cancer. You will be eligible for the MILES Trial. The decision of whether to assume risk by participating in the trial depends on many things, including the rate of progression of your LAM, your current lung function, the extent of your prior breast cancer, etc. This is a difficult question to answer in print.

How long will it take to tell if the drug is working?

Based on the results of the first trial, we are optimistic that effects may be detectable within six to twelve months.

Will it be tested on sporadic LAM or just TS/LAM ?

Both

Would sirolimus actually stop the progression of LAM, slow down the progression or cure or recover? Will it help you from getting worse or does it cure LAM? I realize that it is just being tested, but what are the expectations for this drug?

Our hope is that the drug will stop LAM cells from growing, or even kill LAM cells. That could improve lung function by limiting growth or removing the invading cells from the lung. Once the cells are gone, the hope is that the lung destruction would slow down or cease.

Is there any chance that this drug could improve DLCO in LAM patients?

We don't know yet, but we certainly hope so. This is something the trial is designed to test.

If a treatment effect is seen, will the trial be unblinded so that everyone can have access to treatment? If yes, at what point will this happen?

When 50 patients reach the 1 -year point.

What treatment effect do you want to see?

An improvement in FEV1. We will also look at other lung function measures.

What is the benefit of the MILES Trial in women with LAM who have kidney tumors?
We will not examine AMLs in the MILES Trial, but rapamycin has been reported to shrink kidney tumors in recent medical literature.
Will sirolimus improve the breathing?

That is the hope!

Is the FEV1 score you refer to pre-albuterol or post-albuterol? Which is used to determine eligibility?

Post.

What are the findings from the first rapamycin study? What side effects?

The pilot study was published in the New England Journal of Medicine in January 2008, and the data suggests that sirolimus shows some promise for treating LAM, tuberous sclerosis, and angiomyolipomas (kidney tumors).

Are insurance companies likely to cover sirolimus if studies continue to be encouraging?

If there is convincing proof that the drug works, I believe most insurance companies will cover the cost of the drug.

If my PFTs are normal, can I still get on sirolimus?

You will not be eligible for the MILES Trial, but you may be eligible for other trials.

If the MILES Trial shows it slows down LAM, will we probably still be facing a lung transplant later?

The hope is that we will find a drug that slows progression. Whether it will be partial or complete slowing remains to be seen.

Will we be there overnight or a few days, and will we be paying out of pocket?
There will be an overnight stay involved with the first visit, but travel expenses are funded.
Is there hope that sirolimus may affect the formation of and reduce the complications of chyle in LAM?

Chyle collects when the lymphatic channels are obstructed by LAM cells. There is reason to hope that if rapamycin kills LAM cells, that the lymphatic channels will drain better.

If I'm interested in the trial, but can't complete the study because of transplant, do you recommend that I participate or reserve the spot? What would be best for the study and the Foundation?

You need to act in your own best interest. If you are approaching transplant or being listed, I do not think you should enroll in the trial.

Are you hoping that these trials can slow down or even stop the progression of LAM? Could lung function improve or just stay the same?

We are hoping for all of these!

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