Monday, July 20, 2009

Should you enroll in a clinical trial?

Clinical trials are big business in the United States; indeed, around the world. One group estimates there are 40,000 clinical trials on-going at the present time in the US. Virtually any drug that seeks FDA approval must go through the clinical trial process. This includes already-approved drugs that seek approval for another use; an example of this is our old friend Rituxan, the first monoclonal antibody approved in the US. It is used frequently for CLL, but it was never approved for such a use; instead, it was approved in 1997 for non-Hodgkin's lymphoma. It is undergoing tests now for approval for use in CLL; that's important because any health care 'reform' will limit drug use. It may even make it illegal for Rituxan, or any other drug, to be used off-label.

Any clinical trial needs two things: a new drug or device, and bodies to test them. Cancer, as one can imagine, is chock-full of new drug applications, and clinical trials. Go to the excellent site for the government's clearinghouse for clinical trials (, and you'll find about (about because it changes every day or so) 23,000 trials in the US and overseas that involve some aspect of cancer.

Some trials seem almost silly. There are, for example, a number of trials examining the value of music to soothe the savage cancer patient's breast. There are some that seek to find the value that art has in calming dying cancer patients.

Mostly, however, clinical trials seek to ascertain the dangers and values of drugs in fighting advanced cancer. (There are some trials, of course, looking at treating patients early in the disease; CLL is a particular hotbed of such studies, since previous research has not uncovered a value in starting treatment early, as opposed as to when it is most definitely needed.

Search for CLL trials and (as of this moment) 1209 trials show up. The site seems to list trials that only mention CLL in passing; there are far fewer trials that have CLL as the main focus of study. There are probably fewer than 200 that are of serious interest to the CLL patient.

So, should you enroll in a clinical trial? That is a tough question, but, over-all, I'd recommend you seriously consider it. Why? Because every effective drug for CLL has gone through the clinical trial process, and you'd have first (or second, or third) crack at it. When you have run out of options, that is not a small factor.

(There is also the altruistic nature of trials as well. By joining, you will help future CLL patients have access to proven drugs. But studies have shown that most participant hope to have some benefit as well).

Let's say you've decided to at least look at clinical trials. Are they all created equally? No, of course not. Unless Bach or Picasso really rocks you, you might just say no to music and art clinical trials. You are not going to get cured by such a trial. But what should you look at?

I'll give you my thoughts on the subject, but remember that I'm 'only' a CLL patient, one who has (thank the Lord) outlived his projected lifespan by a number of years, and who is hanging in there as I write.

First of all, you have to decide what drug to look at. This takes research, even if it is just talking to your oncologist. I relied on a CLL expert to guide me in my choice of clinical trials, up to a point. I must admit that, while I am an expert on my own body and how I feel, the CLL expert has seen hundreds of cases, and is more of an expert on how my disease will, in general, progress.

I thought long and hard about my first trial I undertook in 2006. I researched everything the CLL doc told me were my options (and the field is pretty wide open when you are untreated). Yes, I was drowning in green tea back then, but I was still progressing, so my doc and I agreed that I needed something stronger to knock the CLL back.

I also looked at the trials his institution offered. I asked about each of them. I then searched on the top five or six that seemed as though they might be good for me. I printed out study after study, and, using a highlighter, I marked the response rate, the side effects, the burden of treatment (would I have to stay in the hospital) and so on. I then went to and looked at everything that seemed familiar, and a few that didn't. I had been tracking and thinking about clinical trials since I had been diagnosed some eight years before, so I wasn't unfamiliar to the terrain.

Next, I needed to make a decision about what phase trial to look into. A refresher: a phase one trial is a dosing safety trial, meaning they ramp up the drug until unacceptable toxicities are found. A phase two trial is an efficacy trial, that is, does the drug show any activity in the disease. The phase three trial compares the new drug with the standard treatment. (Placebos are never used now in lieu of treatment; it is considered unethical to withhold at a minimum the 'gold standard' treatment, though that hasn't always been the case, in the old, bad days.)

The problem with phase one trials is poetically described in another way to look at these trials: First-in-Man trials. (Many drugs have been used elsewhere, but the name tells a lot.) The phase one trial is given over a range. The first patient usually gets a dose that is far too small to do anything at all. The subsequent patients are given higher and higher doses, until bad things start popping up. Pre-clinical trials give a hint of activity in humans, since they use human cells in culture, as well as the ubiquitous mouse and rat studies.

I have undergone a phase one trial, but I try to avoid them for the reasons outlined above. If you press the trial coordinator, he or she will generally tell you what the other patients in the phase one trial have experienced. But that isn't a foolproof guide. In my phase one trial, the trial coordinator told me to expect flu-like symptoms. (This is such a common description of side effects, it's a little like telling a diner that mongoose or arctic wombat 'tastes like chicken'.) To say I had 'flu-like symptoms' was something like saying the Titanic had a little problem with an iceberg.

I puked my guts out! It was horrible. Yes, I experienced projectile vomit! It was even green, something like the Exorcist (I had a huge helping of spinach quiche the night before.) I've never had such a terrible flu, or if I had, I've blocked it from my memory to protect me from insanity. (Because of my, and others, experience, they now give anti-emetics, or drugs to quell nausea. Thanks, guys, what took you so long?

I prefer the phase two trial. Generally, in a phase two trial you are guaranteed to get the drug (not so in the phase three trial, which is, after all, a comparison trial). The maximum tolerated dose has been established. Anti-nausea drugs have been prescribed. Dosing schedules may been worked out, more or less. Results have been published on the experiences of the first trial (yes, my experience is now part of the record...). You have a better idea of the risks and benefits of the trial.

The phase three trial, as I mentioned above, has the huge disadvantage of not giving the investigational drug to all comers. This is very important in a serious and fatal cancer such as CLL. Why, you could get the standard treatment without going through the qualification process, all of the scanning, all of the prep work, and so on. Some trials do try to 'sweeten the pot' by offering the new drug to 2/3 of participants, instead of a 50/50 split. This is much better for the patient, but this isn't a common practice, for some reason. The best option of all is to give the drug to everyone, and compare their results with historical controls. Hardly any researcher likes this option, which is too bad for the patient community.

My next post will deal with the very real barriers to patient's signing up for trials. It seems to me that not enough researchers are concerned with how we feel about the clinical trial process.

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