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

One Size Fits All—Right Now, But, What If…

The typical clinical trial today involves hundreds or even thousands of volunteers who are fairly similar (have the same cancer with similar stage and similar prior therapy and maybe even similarities in general health). Then two treatments are compared to each other in this large group of patients. If one treatment fares better than the other, that better treatment becomes the new gold standard treatment. That’s good. That’s progress! But it’s certainly not perfect.

So what about the individual patient?

What is lost in this process is knowledge about how these treatments affect individual patients; for example, you. The average benefit seen in a clinical trial is not shared equally by all participants. Some patients are fortunate to have cancers that are particularly responsive to available treatments and these patients may benefit a great deal. Others may benefit a little less and some may not benefit at all. A few may even be harmed by the treatment as they experience unpleasant side effects along with little or no effectiveness.

A clinical trial treatment is judged by how it performed in the entire group of participants and not as much by how each individual patient responded. Over the years, this approach has saved countless lives. In most cases it’s the best we have at the present time. What about the future? What’s on the horizon?

The Big Three New Directions

1 Targeted Therapy. More and more cancer drugs are designed to target specific defects that occur only in cancer cells and not in the normal human body. This is the same process used in creating antibiotics that attack the bacteria and not the human. As a result, antibiotics have been enormously successful. It has been far more difficult to figure out what makes a human cancer cell uniquely different from the regular human cells that it came from. But drugs are now being designed to exploit these newly discovered Achilles’ heels of cancer. For example, Imatinib Mesylate (aka Gleevec) (developed at OHSU) was one of the first such drugs to become mainstream, revolutionizing the treatment of Chronic Myelogenous Leukemia as well as several other cancers.

Targeted drugs have a good chance of being both more effective and less toxic than most drugs currently in use. Targeted drugs are also more amenable to individualized therapy. Since these drugs have a specific target, it is possible to develop tests that examine the cancer and determine if that particular target is present in a specific, individual patient.

2 Personalized Therapy. More clinical trials than ever before are asking patients to consider a biopsy of their cancer as part of the research. For cancers that circulate in the blood this may be possible with just a simple blood sample. In other cases a needle biopsy might be needed to get a sample. Don’t be surprised if you get such a request when you’re contemplating a clinical trial. These tumor samples are being used to better understand which cancers respond to which treatments. Fear of needles aside, this is a good and progressive step in conducting clinical trials and providing benefits for all those with cancer!

It is likely that in the future the multi-thousand patient clinical trials that seek to measure benefit in the entire group may be replaced by smaller studies that focus on subgroups of cancers that have specific treatable defects.

3 Pharmacogenomics. Not only can we not now tell in advance who will benefit from which treatment, we are equally unable to predict who will develop serious side effects. Matching drugs to cancers will require careful biologic analysis of the tumors. Predicting, and therefore avoiding, side effects will require a careful biologic analysis of the whole human being.

While our individual differences are not due only to genetics, many of our differences and those things that make us unique are coded into our DNA. We expect that hidden within that code is the ability to predict how the body will react to various medications and treatments. In the future, we hope to be able to perform very sophisticated laboratory tests that will enable us to predict which treatments will result in the greatest benefit and do the least harm to each individual patient‑‑and for minimal cost. Let’s hope this all happens sooner rather than later!

Post Text Here
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

Tom and Larry interviewed on the radio! Listen on Saturday the 18th

Larry and I got a chance to sit down with a radio reporter for an extended conversation about cancer clinical trials.  I biked in the rain to the studio while Larry called in from his sunny patio in the southern Arizona desert.  You can tell right away who is the smarter partner in this writing partnership!

If you would like to listen in, you have two options.  In the Portland metro area, you can tune in to KXL 101 FM.  If you are anywhere else in the world, the show will be streamed live online at  http://www.kxl.com/pages/main.

The show airs at 8 AM Pacific Time (11 AM Eastern Time) on Saturday, February 18th.  


UPDATE:  If you missed the show and would like to listen, click here.

To put a smile on your face see Larry's latest cartoon


(c) 2012 Tom Beer and Larry Axmaker

The big trends in medical treatments for cancer

Medications are the mainstay of treatment for those cancers that by their nature or because they have spread, cannot be removed surgically or eliminated with radiation.  Medical treatments are also often added to surgery or radiation to kill the few cancer cells that may have escaped and reduce the chance of cancer coming back.  The broad trends that are driving research into new medications for cancer include:

·        New chemotherapy drugs and combinations of drugs

·        New ways to manipulate the hormones that drive certain cancers (primarily breast and prostate cancer)

·        More specific and targeted therapies that are sometimes referred to as “smart bombs.”  These types of treatments are designed to attack very specific mechanisms that drive cancer growth and spread.  A variety of technologies make targeted therapy possible.  Some are artificial antibodies, synthetic small chemical molecules, and gene-directed therapies

·        Harnessing the immune system to fight cancer

·        All cancer therapy is likely to become more personalized (individualized) with treatments selected to match each person’s unique cancer.