Advanced Prostate Cancer--Trials Don't Live Up to Expectations

 Dr. Tom Beer and Dr. Joshi Alumkal, of Oregon Health and Science University,  published an editorial in the July 12, 2016 issue of the Journal of Clinical Oncology questioning the value and accuracy of recent Clinical Trials using Docetaxel (a chemotherapy drug) to control symptoms and prolong life in metastatic castration-resistant prostate cancer (mCRPC) patients. Here are some of the topics they covered.

Since 2004 numerous Phase III clinical trials have used Docetaxel as one part of clinical trials looking for survival advantage in men with advanced prostate cancer. More than half of the trials failed to produce positive results and others produced very weak results. The authors explore how and why this has happened.

Some trials produce 'statistical' success (e.g. significance)  but not much 'clinical' benefit (e.g. a survival benefit of only a month or two). With such a high rate of Phase III failures, it makes sense to change the design of these clinical trials. The authors suggest:

1    Include the patient in the planning process. What do these men want and expect? What would be a positive outcome for them? What would make them want to volunteer for a clinical trial?

2    Identify and focus on patients most likely to benefit from a particular drug or treatment. Then design small studies including only those patients.

3    Determine what success is--improvement in survival, better quality of life, lower risk of toxicity, etc.

There have been too many failures in mCRPC phase III clinical trials to justify continuing the same procedures again and again. Trials are costly, patients are exposed to potentially toxic agents with little benefit, and marginally effective drugs may be moved toward approval. Studies should focus on providing the greatest likelihood of significantly improving the lives of patients.



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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

FDA approves new lung cancer drug

The lung cancer drug erlotinib (Tarceva) treats a certain type of non-small cell lung cancer. 10% to 30% of lung cancer cases fall into this category. In a randomized phase III clinical trial, erlotinib, in tablet form, was compared to the current best treatment; platinum-based doublet chemotherapy.

The trial measured and compared progression free survival (PFS) and overall survival (OS). The experimental drug performed significantly better in both measures. The median age of participants was 65, more than two out of three were women, and most had never smoked. There was tumor shrinkage in 65% of those taking erlotinib and 16% of those receiving chemotherapy.

This is another example of the power and efficiency of the clinical trials process. As a result of a clinical trial a new and improved treatment is now available.

Erlotinib is sold by Genentech as Tarceva. You can find more information on their website.

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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

Enzalutamide shown to extend survival in prostate cancer

A video summary of my presentation at GU Cancers Symposium in San Francisco in the last days of January 2014.



 From http://ecancer.org.  To go the ecancer site, click 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

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

Clinical trial phases from the participant's point of view

There are many types of clinical trials.  Most commonly, they are divided into phase I, II, III, and sometimes IV.  The phases refer to the phases of testing of a new drug in humans. Some our previous posts describe the various phases and discuss phase I trials and phase III trials in more detail.  Here we would like to share with you page 47 from our book, where we provide a succinct summary of the advantages and disadvantages of each trial type, from the perspective of trial participants.  The table shown below may not apply to every single trial, but it does give you a quick and straight forward basic guide.

If you would like to download a PDF of this page you can do so here.  Feel free to share it.

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

Cancer Clinical Trials: How to get the new treatment

The most promising new treatments are tested in randomized trials, also known as phase III trials.  Usually a coin flip‑‑more likely a computerized equivalent‑‑decides whether each participant gets the new treatment or the current standard.  Since the new treatment wouldn’t get this far in research if it were not promising, it is not surprising that many people want to get the new treatment and not the old one.  Is there a way to do that?

No there isn’t at the beginning, and it is good to remember that when a randomized trial starts, we don’t know if the new treatment will really be better than the old. We all hope that it will, but history teaches us that some will and some will not.

There are four ways, however, that clinical trial participants may be able to get access to the new treatment even after a coin flip assigns them to the standard treatment:

• Some randomized studies allow a crossover. This is a situation in which participants receiving a randomized treatment can later receive the treatment that was given to the other group of patients in the study.
• If the new treatment turns out to be better while the study is under way, the trial is often stopped and the new treatment may be made available to all the study participants who did not receive it in the first place.
• Once a study is completed and the new treatment is proven better, some companies offer a Compassionate Use Protocol, Early Access Program that makes the drug available on a limited basis until the drug gains FDA approval.  These are often available at the research centers that carried out the phase III study.
• When a new drug is clearly a winner, FDA approval can come quickly (despite the commonly held belief that it takes a long time).  The FDA has approved drugs within several months of study results showing a compelling benefit to cancer patients.

While there are no “tricks” one can use to assure being assigned to one treatment group or another, there are a number of ways to eventually get access to a new cancer drug regardless of what the coin flip decides for us in the first place.  This is particularly true if the new treatment is confirmed to be a real improvement for cancer patients.

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


(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. 


External links in this post may expire in 3 months.

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


(c) 2012 Tom Beer and Larry Axmaker

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.



To put a smile on your face see Larry's latest cartoon
(c) 2012 Tom Beer and Larry Axmaker

New Phase III Cancer Clinical Trials - December 2011

     Our search, carried out on December 22, showed 22 new phase III trials registered in the last 30 days.  We will highlight two that explore immunotherapy in two very different contexts.  
     The first trial compares the use of the patient's own stimulated killer cells (a part of one's natural immune system) to the use of chemotherapy in advanced lung cancer.  The study is being carried out in China, so it is likely inaccessible to most US cancer patients, but it is a good example of how immunotherapy continues to be a major direction for cancer clinical trials.  
     The second trial tests a vaccine product called NeuVax (TM) to determine if the vaccine can prevent the relapse of breast cancer.  Patients who have early stage node positive breast cancer that has low or intermediate expression of the HER2 protein are eligible.  Experimental treatment follows the completion of standard treatments such as surgery, radiation, and chemotherapy.

     You can click on the hyperlinks above to see each individual trial or click here to learn more about both of them:

New immunotherapy trials Dec 2011 (click here - link expires March 21, 2012)
     To see all 22 new phase III trials registered in the last 30 days, click here:
All new phase III cancer trials Dec 2011 (click here - link expires March 21, 2012)