NCI-MATCH Trials…Something New

In a recent press release, the National Cancer Institute outlined a new cancer clinical trial program, focused on linking targeted cancer drugs to gene abnormalities. MATCH stands for Molecular Analysis for Therapy Choice.

The trial seeks to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.

NCI-MATCH is a phase II trial with numerous small substudies (arms) for each treatment being investigated. It will open with approximately 10 substudies, moving to 20 or more within months. 

The NCI-MATCH trial has two enrollment steps. Each patient will initially enroll for screening in which samples of their tumor will be removed (biopsied). The samples will undergo DNA sequencing to detect genetic abnormalities that may be driving tumor growth and might be targeted by one of a wide range of drugs being studied. If a molecular abnormality is detected for which there is a specific substudy available, to be accepted in NCI-MATCH patients will be further evaluated to determine if they meet the specific eligibility requirements within that arm. Once enrolled, patients will be treated with the targeted drug regimen for as long as their tumor shrinks or remains stable. Overall, trial investigators plan to screen about 3,000 patients during the full course of the NCI-MATCH trial to enroll about 1,000 patients in the various treatment arms.

Adults 18 years of age and older with solid tumors or lymphomas that have advanced following at least one line of standard systemic therapy, or with tumors for which there is no standard treatment, will be eligible. Each arm of the trial will enroll up to 35 patients. The trial’s design calls for at least a quarter of the 1,000-patients enrolled to involve people with rare types of cancer. 

For several years now there has been much discussion of using targeted therapies to treat cancer—this will be the first big study to actually do it.

“NCI-MATCH is a unique, ground-breaking trial,” said Doug Lowy, M.D., NCI acting director. "It is the first study in oncology that incorporates all of the tenets of precision medicine. There are no other cancer clinical trials of this size and scope that truly bring the promise of targeted treatment to patients whose cancers have specific genetic abnormalities. It holds the potential to transform cancer care.”

Since many gene mutations in tumors are infrequent or unique, screening for individual mutations is not cost-effective or efficient in clinical trials. Instead, NCI-MATCH will use advanced gene sequencing techniques to screen for many molecular abnormalities at once. Large numbers of patient tumors will need to be screened because most gene mutations occur in 10 percent or less of cancer patients. Most patients are expected to have one, or at most two, treatable mutations in their tumors. By having multiple treatments available for these genetic abnormalities in a single clinical trial, several different study drugs or drug combinations can be evaluated simultaneously.

The cancer treatment drugs being used in NCI-MATCH include both U.S. Food and Drug Administration approved drugs as well as investigational agents that are being contributed by a number of pharmaceutical companies. Most of the arms in the trial will incorporate single-agent drugs that are either commercially available or are still being tested in clinical trials. However, a few arms will contain combinations of drugs for which there are enough safety data and evidence that they might be active against a particular genetic abnormality.

Screening has not started (starts in July 2015) and there is no specific timeline. Participants will continue to take the trial drugs until their cancer no longer responds to the medications. This approach may be the template for future targeted treatments. Specific drugs for specific gene mutations is a step forward. Watch for results—sometime soon, I hope.

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To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Nobody in a clinical trial wants to be given a placebo, whatever that is…

“Placebo” is often used in a negative way. But that’s not necessarily true. Placebos are sometimes used in clinical trials. A placebo is a biologically neutral substance packaged to look like the real drug. Although often referred to as a sugar pill, many placebos are not even pills. They are simply inactive compounds packaged to look, feel, and appear like an active drug. They may be an injection, IV infusion, capsule, a cream, an inhaler, a skin patch, or take any other form that is used by an active drug.

Placebos are used when the purpose of the research is to compare different approaches to treatment. The placebo helps ensure that the study is double blinded which means neither the doctor nor the patient knows which treatment is being administered. Many cancer patients are understandably concerned that they might get a sugar pill instead of a real treatment. This is often the first question the physician researcher hears when a clinical trial is brought up as an option, “Will I get the real thing or just a sugar pill?”

When placebos are used

The fundamental principle that defines when placebos are appropriate is rather simple: if you have cancer, and a treatment that works is available, a placebo cannot be used instead. Period‑‑end of story. Research is not and cannot be about withholding effective treatments from patients with cancer. A placebo can be used in two research situations:

1          There is no effective treatment and the standard treatment would be observation or perhaps supportive treatment (treatments designed to lessen symptoms but not treat the disease).

2          There is an effective treatment and this treatment is being given to all patients in the study. The placebo is being added to the known effective treatment to allow a comparison between the standard treatment and a combination of the standard treatment plus a new drug of unknown effectiveness.

The Placebo Effect (this is kind of weird)

The most mysterious benefit of having a placebo in a study is that placebos actually do work! Now you may think we are completely losing our minds (always a possibility), but it is true! The degree to which placebos work varies considerably depending on what disease is being studied, but it stands to reason that if we are going to devise a fancy, expensive, patented new drug with an unpronounceable name, it should produce results better than a mere sugar pill. According to the American Cancer Society, placebos have an effect on about one in three patients. Often the result is a reported improvement in a symptom or in quality of life. Sometimes it could actually be a new side effect. The mechanisms through which placebos work may represent, to some extent, the importance of the mind-body connection.

A placebo can reinforce patients’ belief that they will get better and so they actually do. In general, placebo effects are seen as symptoms or things people feel. The actual shrinkage of cancer tumors would be extraordinary. Nevertheless, many studies of new cancer drugs look beyond tumor shrinkage and length of life following a cancer diagnosis. They examine quality of life, symptoms of cancer, and side effects of the drug. Placebos allow us to see the true picture of what a new drug can offer beyond what you could get from a sugar pill.

There’s more to learn about the placebo. Watch for the next chapter!

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To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Back to basics

Since starting this Cancer Clinical Trials blog in 2011, we have covered a lot of materials, provided links, and talked about the latest experimental drugs. We believe that every once-in-a-while it is a good idea to go back and review clinical trial basics.

What is a clinical trial?

Clinical trials are highly organized and complex experiments to test and compare new therapies in human volunteers who may or may not have cancer. Promising treatments go through a series of tests to make sure they are safe, effective, and have minimal side effects. Testing in humans is the only way to find this information. All the Standard Cancer Therapies currently in use were developed and proven effective in clinical trials. Then they were approved for general use by the FDA (U.S. Food and Drug Administration).

Why would you want to participate in a clinical trial?

You may consider joining a clinical trial if no appropriate standard therapy is available; the current standard treatment leaves room for improvement; or because you don’t need treatment right away because your cancer is slow-growing and you would like to try something new.

Many new ideas are being evaluated in clinical trials today--for a broad variety of cancers. Cancer treatment has advanced and improved rapidly in recent years.There are more cancer survivors than ever before. But many experimental cancer drugs and treatments have not yet been tested in humans because there are not enough clinical trial volunteers.

We will continue to provide a variety of information to increase your understanding and maybe even help you make personal health decisions. We welcome your questions and comments. 

To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

The West Coast Prostate Cancer Dream Team

Research Dream Team Studies Prostate Cancer Treatment Resistance from Patient Power® on Vimeo.


To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Can the immune system remember?

The study we discuss here is not "ready for prime time" but it does report some exciting findings that suggest that immunologic therapy for cancer can produce long term immune memory



To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Larry and Tom interviewed: prostate cancer, clinical trials, and our book

We were interviewed by the blog JoinClinicalTrials.com a while back.  Here we share the interview with you:

1. How did the two of you become colleagues/friends and what was the inspiration behind your blog? 

We met in the prostate cancer clinic as patient and physician and forged a friendship over the years.  The blog, along with the book was inspired by a strong desire to share knowledge about clinical trials with people who are living with cancer and who are called upon to make decisions about their cancer care. 

 2.  You are co-authors of the book Cancer Clinical Trials. Please tell us about it and what prompted you to write a book about clinical trials?

For 15 years now I have been deeply involved in clinical trials.  I have talked to thousands of cancer patients about hundreds of clinical trials.  Despite the fact that we spend a lot of time with each potential participant, I frequently had the nagging feeling that in the course of a clinic visit, or even several, we could never quite do a good enough job sharing all the knowledge I wanted to share with my patients.  The book was the only way to get this done.

 3. Dr. Beer, could you please address some of the common misconceptions and fears that people have in regards to clinical trials?

Well, there are many, and we cite examples throughout the book of misconceptions we have run across.  I think the first thing people worry about is that they will get a placebo and not a real drug.  We talk a lot about the way placebos are used in research in the book.  I think that is the area where there are the most misconceptions. 

There are many other areas.  For example, many people think that clinical trials are only appropriate when all other options have been exhausted.  That is not true at all.  Clinical trials are seeking to improve care across the entire spectrum of the disease and may be worthy of consideration at various points in the battle with cancer.

 4.  (Dr. Beer) Many people think that clinical trials are an option only after they have tried every other treatment for their cancer; however, is that really the case? Is it possible for patients to participate in trials in different stages of their disease?

No question about it.  Clinical trials seek to improve care in all situations including front line care.  The trials may be different in patients that have good standard treatment options.  For example, the standard treatment may be included for all patients and the new drug is added to it. 

But without clinical trials that test even the most fundamental cancer treatments, we would not have made the advances we have.  For example, breast cancer is often treated with surgery that removes only the cancerous lump and spares the breast.  Clinical trials that proved this was a sound approach are responsible for women being able to keep their bodies intact through cancer treatment.

More of our interview in the next post.

To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.
(c) 2013 Tom Beer and Larry Axmaker

Myths and truths about cancer clinical trials

Myth #1—Cures already exist for many cancers but drug companies are keeping them under wraps in order to make even higher profits when they are released or to profit from current less effective drugs.

Truth #1—You gotta be kidding! The world drug market is large and very competitive and no pharmaceutical company is going to give up a chance to market a great product. Holding back could give other companies a chance to develop and market a similar drug.

Myth #2—Many experimental cancer drugs in the U.S. have already been tested and approved in other countries.

Truth #2—Sometimes drugs ARE available first in other countries. But the U.S. is by far the world leader in cancer research and new drugs are more often than not available to Americans first.

Myth #3—If I join a clinical trial, whether it is successful or not, I’ll be disqualified from ever participating in a trial again.

Truth #3—Nope. Many people with cancer participate in two, three, or more trials in their lifetime. This author (LWA) has participated in three clinical trials and is considering a fourth. Your previous history, including clinical trials, could be considered when you apply for a new clinical trial. Do your homework and make sure joining a trial is in your best interests.

Misconception #4—In almost all cases, drug testing can be done in test-tubes, with animals, and by computer simulations. Testing on humans is seldom necessary.

Answer #4—Don’t we all wish! It would certainly be faster and cheaper if people were not needed in the drug approval process. But, in fact, testing on humans is currently the only way to determine proper dosages, the effects of side effects, and whether or not the drug actually cures or manages cancer.

Myth #5—Drug companies pay hospitals and doctors a lot of money to ensure they get the best possible results from clinical trials. The better the results, the higher the payments.

Truth #5—The pharmaceutical companies often pay for some or most of the costs of a clinical trial. These payments are never linked to the results of the trial.  And, at the end of the day, academic centers do not make a profit on clinical research.  There are several layers of safeguards to make sure trials are conducted scientifically and accurately.

Myth #6—Most clinical trials only accept participants who have the least serious and dangerous types of the cancer being tested in the trial in order to improve the chances of getting good results.

Truth #6—Cancer treatment drugs are developed for all levels and stages of cancer. Some trials, however, may exclude patients with serious heart, lung, kidney, or liver diseases to protect them from unknown side effects. After a drug is proven successful and safe, these high-risk people may be included in further studies.

To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Our man in Russia....a glimpse at the international nature of clinical research

A few years ago, we had the opportunity to host a 27-year old Russian oncologist in Oregon. This was a part of an international exchange sponsored by our professional society, ASCO.  Young oncologists from around the world were hosted by American institutions for a week to get some experience with research conducted in the US.  Who would have thought that our guy, Ilya Tsimafeyeu would become the CEO of RUSSCO, the Russian counterpart to ASCO, the American Society of Clinical Oncology.  

It was fun to see a recently interview with Ilya, or shall I say, the CEO.  Take a look at it here if you would like a glimpse of how things are going in Russia.

To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Gold Nanoparticle Therapy to be used in first clinical trial

Like most of us, you have probably never heard of gold nanoparticle therapy. That’s not surprising. It's a new treatment that will be used for the first time in a cancer clinical to treat lung cancer. The process was invented by biomedical engineers, Naomi Halas and Jennifer West, at Rice University in Houston, Texas. The trial will be conducted by Cancer Treatment Centers of America.

When these nanoparticles were first tested in mice, the result was tumor remission in 100 percent of the experimental subjects.

The nanoparticles consist of microscopic balls of silica (glass) encased in a thin shell of gold. These nanoparticles are injected into the blood stream and absorbed by tumors—not healthy tissue.

After 12 to 24 hours, when the particles have been absorbed by the tumor, an infrared laser is used to heat the particles and destroy the tumor cell. Tumors are damaged or destroyed with minimal effect on healthy tissues.

The trial, approved by the FDA, will be conducted by Mark Lund, MD, Director of Interventional Pulmonology, Bronchoscopy & ICU at Eastern Regional Medical Center. Additional trials are planned for metastatic head and neck tumors and prostate cancer.

Successful results from these trials could provide new and minimally invasive treatment for some common cancers.

To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

Do people know about clinical trials? Some surprises

We often say that fewer than 5% of adults with cancer participate in clinical trials during the course of their cancer therapy.  What does the bigger picture look like?  A recent publication describes the results of a 2011 survey.  A nice summary of the key findings can be found in this article.  11% of adults reported ever participating in medical research - surprisingly higher than the percentage of cancer patients.  A full 64% were aware of research opportunities.  

Participation and awareness both were more likely among folks with higher incomes, more education, among older people, people suffering from chronic conditions, and people who live close to large clinical research centers.

Although one would think that the internet would be the number one source of information about medical research (and our blog readers might think so too), participants in the survey cited television as the most common source at 53%!  46% cited radio, 44% newspaper ads, 22% the internet, and 21% learned about a research opportunity from a pamphlet in their doctor's office.  

All in all, it looks like folks living with cancer participate in medical research less than the general adult population - a surprise.  And the internet appears not to be the number 1 (or even 2 or 3) source of information about medical research for US adults - a bigger surprise.  This may change as the internet gains prominence, but we should not assume that "old media" no longer matter in spreading the word about medical research opportunities.  

To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

What are the next steps after being accepted into a clinical trial?

Acceptance into a clinical trial begins with the consent process.  Risks and potential benefits, as well as other options are explained by your physician or research nurse and also presented to you in writing in the Consent Form – typically a lengthy document.  Once you have been fully informed and have consented to the treatment, the next step is to complete the pre-treatment evaluation.  This includes a visit with your doctor or nurse, blood tests, scans to determine the extent and location of your cancer, and potentially other tests mandated by the study.  At this stage, it is still possible to be “uninvited” from the study.  This happens if a test result shows that you don’t meet all the criteria to safely participate.  Once the pre-treatment evaluation is complete, the study treatment begins. 

For more questions and answers about clinical trials, visit the Talk about Health website.
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

How is being in a clinical trial different from getting regular treatment?

In many ways, being in a clinical trial is similar to receiving standard treatment.  There are regular visits, blood tests, scans, and a cancer drug – or several – are given on a set schedule.  Side effects are monitored and adjustments are made to minimize them.  There are some differences.  As much as cancer treatment programs tend to be fairly rigid and structured, clinical trials are even more so.  Everything that happens follows a precise recipe.  There may be additional tests or surveys to fill out that would not be a part of standard care.  Some of these may include much more extensive monitoring – for example serial blood draws to measure drug levels in detail during a 24 or 48 hour period.  It is also likely that less is known about the drug or drug regimen that is being tested than standard care.  Outcomes in cancer treatment are never certain, but participating in a clinical trial involves a greater degree of the unknown.  

For more questions and answers about clinical trials, visit the Talk about Health website.
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

How many patients typically participate in each phase of the clinical trial?

Clinical trials are often described as phase I, II, III, and sometimes phase IV.  The number of participants varies greatly depending on the phase of investigation, but also depending on the cancer type, situation, and expected outcome.  Phase I trials are principally charged with determining the safe and optimal dose of a new drug or drug combination.  Such trials may involve 20 to 40 patients.  Phase II trials are where the potential of a drug to be effective is first evaluated.  Typical phase II studies range in size from 50 to 250 participants.  The higher end of that range is more common in randomized phase II studies where 2 or more doses or drug combinations are being examined side by side.  Phase III trials are the ultimate test of a new treatment.  Participants are randomly assigned to the new treatment or the current standard.  These trials involve hundreds and sometimes thousands of participants.  The number of participants needed is determined by the question being asked, the expected magnitude of the difference between the two treatments, and the percentage of patients who are expected to experience the outcome being measured.  For example, trials that seek to reduce the risk of cancer recurrence are often very large in part because many of the participants (thankfully) don’t suffer a recurrence at all.  A large number of participants are therefore needed to make sure that enough of them have a recurrence so that a difference can be detected.

For more questions and answers about clinical trials, visit the Talk about Health website.
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

In the US, who decides what cancer research is funded and how much funding each project receives?

There is no single authority that allocates cancer research funding.  Each funder has a process.  The largest source of funding for research is the National Institutes of Health which uses a peer-review process.  Panels of researchers review and rank research proposals.  This is probably the best process we have.  It is independent and invites the best thinkers to drive it.  Sometimes this process does, however, end up emphasizing funding for ideas that fit well with today’s thinking.  Unconventional ideas may not always be appreciated by peer scientists.  The pharmaceutical industry is the other large source of funding.  It allocates funding largely based on it’s view of market opportunities for new drugs, although industry also provides funding for independent research.  Many private foundations, and government agencies other than the National Cancer Institute are also important.  They generally follow the peer-review process or some variation on it.

For more questions and answers about clinical trials, visit the Talk about Health website.
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

What metrics are typically used to determine if the drug is successful?

The ultimate success of a new drug or drug combination is judged by the “safe and effective” standard.  Both of course are examined in context.  Safe often means safe enough – or no less safe than what we have today.  Some cancer treatment have severe side effects – but because their benefits are judged acceptable – they are approved.  Effective means that cancer patients benefit in a meaningful way.  This often involves living longer.  When survival is not impacted, meaningful quality of life improvements are required.  In some situations, cure rates are the measure of success.  Survival benefit, which is the most common measure of success, can take a year to several years to determine.

For more questions and answers about clinical trials, visit the Talk about Health website.
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker

How to keep track of the latest clinical trials that one may be eligible for

The single most complete resource for clinical trials in cancer is offered through the NCI at www.cancer.gov.  Clinical Trials are listed under the Clinical Trials and the Find a Clinical Trial tab on the www.cancer.gov website.  Detailed instructions on how to use this search tool are available on the website.  We also provide a discussion of that in our book, Cancer Clinical Trials.  Once you set up a search that fits your specific situation, there is an easy way to track the latest trials.  The trial status component of the search form allows you to check the new trials box. This will show you only trials added in the last 30 days. This feature is very helpful if you want to track any new trials that are activated without going through the entire list every time.  A useful strategy is to do a thorough search for clinical trials once and then repeat the same search with the new trials box checked every 30 days.  This way, one can be sure not to miss anything new. 

For more questions and answers about clinical trials, visit the Talk about Health website.
To put a smile on your face see Larry's latest cartoon.
To learn more about clinical trials, take a look at our book.

(c) 2012 Tom Beer and Larry Axmaker