Guest Post: Clinical Trials Are a Perplexing Issue for Many Patients

We asked a number of thoughtful people to read a pre-publication copy of our book and give us some feedback.  We are incredibly fortunate to have the counsel of Dan Zenka.  After looking at the book, Dan posted the following on his blog and allowed us to re-publish his thoughts here to share them with you.

Dan Zenka is senior vice president of the Prostate Cancer Foundation, the world’s leading private supporter of research for a cure. Two years after joining PCF, Dan was diagnosed with his own case of prostate cancer. Following a radical prostatectomy, it was determined that he had metastatic disease. He has undergone seven weeks of radiation therapy and is currently on two to three years of hormone deprivation therapy. Just days after his diagnosis, Dan started his own cancer blog, www.mynewyorkminute.org where he discusses a range of issues related to navigating prostate cancer and is read by a growing audience of men and their caretakers around the world.  What follows are Dan's words:

Despite the prospect of receiving one of the latest new drugs that might extend survivorship, a lack of understanding and access, among other issues, leave many saying “I’ll pass.”

Clinical trials are a crucial component of a drug’s development and ultimate approval by regulatory agencies. On the upside is the chance that a participant will benefit from the therapeutic effect of a new compound that can add months if not years to their life. On the downside, a patient might delay more immediate, already-approved treatments only to find out that they were in the placebo arm of the study and are left to resume their original plan. And then there is the real bonus–finding yourself in a Phase III trial in which the drug meets the study’s pre-specified interim efficacy stopping criteria, demonstrating a clinically meaningful and statistically significant improvement in overall survival compared to the placebo. In that case, something called the Independent Data Monitoring Committee (IDMC) recommends that the

The year they will crack cancer?

     This is the provocative title of a wonderful article by Geoffrey Carr in The Economist.  The cost of sequencing a human genome has come down from billions to thousands of dollars over the last two decades.  Genetic mutations are the cause of many cancers.  Normal human cells are “well behaved” and grow only when needed, but when they lose the breaks on their growth, they become pre-cancerous and finally develop into invasive cancer.  See our post on the hallmarks of cancer.  We know what a few of these genetic defects are.   

    This knowledge is important.  It has already produced revolutionary new therapies like Gleevec for chronic myelogenous leukemia.  The trouble is that cancer cells acquire many such defects and to make matters worse, carry many other defects that really don’t matter much.  Today we often find ourselves staring at one cancer defect that we can target with a drug but having little knowledge about what else in the same cancer is propelling its growth.  To answer these tough questions, we must decode all of the mutations in many cancer samples.  Mutations that occur over and over again in many individual cancers will likely be the important ones, the drivers.  Those that show up at random, are probably the bystanders.  

     To tackle this enormous task, a group of sequencing labs around the world has formed the International Cancer Genome Consortium.  They intend to sequence several hundred samples of 50 different cancers.  As of last fall, 39 labs had signed up and more will come.  The work is to be finished by 2015, but expect results to start coming in by the end of 2012.  

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(c) 2012 Tom Beer and Larry Axmaker

Placebo makes it big! On national TV

The history of placebos and the placebo effect spans thousands of years.  We wrote about them recently.  CBS News' 60 Minutes recently ran an fascinating story about placebo effects in the treatment of depression.  The bottom line is that placebos offer important benefits to patients with depression, especially mild to moderate depression.  There have been many placebo-controlled studies in cancer.  Tumor responses are very rare and aren't fully understood.  Sometimes they may represent an immune system effect.  Improvement in symptoms is more common and may represent an effect of the mind-body connection.  The video program is worth a look and, like all 60 Minutes pieces, not without controversy.





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(c) 2012 Tom Beer and Larry Axmaker

New Phase III Clinical Trials February 2012

     This month's search revealed 29 new phase III clinical trials registered in the last 30 days.  We are consistently seeing around 1 phase III trial being added to the national registry per day.  
     We would like to highlight two interesting studies that are brand new.  The COMET-2 study compares cabozantinib (XL184) with mitoxantrone in the treatment of men with advanced, metastatic prostate cancer who have already received standard chemotherapy.  The main focus of the study is relief of cancer-related pain, although both drugs are designed to fight cancer.  This does not mean that the treatment may not also provide other important benefits including control of cancer and perhaps extension of life.  Instead it illustrates that quality of life is increasingly considered in cancer clinical trials.
     The second remarkable feature of this trial is that XL184 is a modern targeted drug and it is taking on a traditional chemotherapy drug head to head.  This is illustrative of the overall trend in the field, where newer drugs that seek to exploit specific proteins in cancer and are more precise than traditional chemotherapy are increasingly prominent.  
     The second study we find fascinating is the BALANCE study which uses a fluorescent dye to guide surgery for brain tumors.  The procedure involves taking a natural compound by mouth 3 hours before surgery.  The compound is taken up by glioma (brain tumor) cells and causes the tumor to glow with a red hue under a special blue light.  Studies from Europe suggest that the chances of a complete resection may be considerably better with the use of this agent than with a conventional surgical approach. 


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(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.

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(c) 2012 Tom Beer and Larry Axmaker

Are Cancer Clinical Trials going to the dogs?

Canine clinical trials are helping test new treatments that might work for humans. If that happens, we may be thanking Max, Queenie, or Pal at some future date.

A team of scientists at the National Cancer Institute in Bethesda, Maryland is conducting canine cancer clinical trials. Other similar trials are being conducted at other centers. Cancer is a leading cause of death in dogs. Why is this approach unusual‑‑aren’t animals used to test drugs all the time?

• The dogs are family pets that have been diagnosed with cancer by their vets and referred to the clinical trials. More than a million dogs are diagnosed with cancer every year—and that’s just in the U.S.
• Cancer in dogs is often very similar to cancer in humans.
• Experimental medicines can be started sooner than in humans, if the owners agree. And results are known sooner because cancers grow more rapidly in dogs.
• Many owners are happy to get the newest experimental treatments for their beloved pets.
• And researchers get important data that might help treat cancers in humans.
• The dogs that are treated with experimental drugs are often helped and able to live a longer and healthier life with their human families.
• Unlike many animal trials, no dogs have cancer purposely implanted to enable studies. These dogs are treated after they naturally contract cancer.

Canine trials have focused on bone cancer, lymphoma, and melanoma—common cancers in humans. These trials have the potential to help both dogs and humans—a win-win if there ever was one.

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(c) 2012 Tom Beer and Larry Axmaker

Phase I cancer trials: the newest drugs, but not for everyone

Access to the latest and newest drugs sounds very compelling, but it isn't always the best choice for all cancer patients.  The latest drugs are first tested in phase I studies and these studies are not for everyone.  Phase I studies (clinical trials) may be appropriate when the cancer is not responsive to standard treatments or no standard treatments exists. Since we don’t know much about how successful the new drugs in phase I studies will turn out to be, proven treatments should be tried first.

Classic phase I studies are designed almost exclusively to test the safety of various doses of a brand new drug. The drug has already been analyzed and evaluated in laboratory animals, and has shown promise for the treatment of cancer in the laboratory.  Effectiveness may also be evaluated, but this is secondary to the primary goal of documenting side effects and safety and sorting out what the optimal dose of the drug will be in human beings.

There are examples of drugs that yielded spectacular results even in their first phase I trial, but for most participants that is not their experience.  

The phases of cancer clinical trials

Clinical trials are often divided into phases.  These actually refer to phases in the process of developing a new drug.  Here is the scoop:

·        Phase I studies are small, and their goal is to determine the optimal dose of a drug, or combination of drugs, that can be given safely. This does not mean entirely free of side effects, just an acceptable or manageable level of side effects.

·        Phase II studies are also relatively small and may involve anywhere between 30 and several hundred patients. They are the first studies designed to test how effective a new treatment is against cancer.

·        Phase III studies are large and may involve thousands of participants. They compare the most promising new treatments to the current standard.

·        Phase IV studies usually collect more safety and effectiveness information on new therapies after the U.S. Food and Drug Administration has approved them.



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(c) 2012 Tom Beer and Larry Axmaker