What everyone should know about phase 1 trials - part 1

When you step into the relapse world, all of a sudden, you are faced with phase 1 trials. The problem with phase 1 trials is that we, as parents of children with neuroblastoma, see them as therapeutic - in other words we see them as hope to make our kiddos better. The problem is that, by their very nature, these trials are not aimed at producing a result. The true intent of these trials is not to cure the cancer. In fact, it is not even to help it. Phase 1 trials have one mission in life. That is to see how much of a drug or combination of drug we can give without creating horrible side effects.

Do not make the mistake of assuming that these trials are designed for the benefit of your child.

THEY ARE NOT!

The trick, however, is to figure out how to use them so that they will work for your child's benefit!

I do not mention phase 1 trials in this context to keep people from participating in phase 1 trials. I believe they are extremely important. After all, Sydney was a part of one. They are a necessary step in trying any new drug or combination. We must first see if it is safe enough to give and how much of it we can give safely. This "test" has to be performed somewhere and on someone. That is the purpose of the phase 1 trial.

This "purpose" is not because the researchers do not care about our children. It is not because the government is beating down on the man. It isn't because of bureaucracy or because people don't understand.

It is simply because, if we are ever going to make any discoveries of new drugs and therapies, we must first define their safety in some test subjects - yes, our kiddos. It is a necessary evil. It has to happen.

Again, the trick is still to figure out how we can use them to our child's advantage.

So, why do I tell you this? Well, this is one of the most common issues I see with parents facing phase 1 trials. Often many of the most important points are missed. This is critical because even though phase 1 trials are not designed to be therapeutic they still can provide benefit and we, as parents, must understand them well enough to evaluate them. We must understand all of the issues related to the trial design and the drugs preclinical and adult track record to make the best decision possible. This is often often complicated by the fact that our children have a very small window to start the next therapeutic option. Chances are we will never have perfect timing on any one trial. Thus, we have to be able to evaluate them quickly and prioritize them so that we can make the best choice possible. Often the chance of a particular drug or combination working in a phase 1 trial has less to do with the drugs and more to do with the timing. That is the critical determining factor. Does your child have disease that will be susceptible to the drug or combination? Is he or she eligible for the drug at a time when the drug is most likely to work. Is the drug at a dosing level where it is even expected to work? Is the trial even open when you need it or is it in a planned closure to review toxicity? This last point is one of the most overlooked. Most phase 1 trials have planned closures at the end of each dosing level to evaluate toxicity. This means that during these times no one can become part of the trial until it is reopened. Did you know that some of our most effective phase 1 trials actually spent more time being closed than open. Again, this is not because the researchers are mean and ill hearted. This is federally regulated stuff. Our investigators don't have a choice. It is simply a reality that we must interpret and determine how it effects our child.

Regardless, my point is that timing is usually a bigger issue than anything else in evaluating a phase 1 trial and in determining the likelihood of whether it will work for your child. To me, it is almost more important than the drug(s) itself(themselves).

So I could write a series of entries about phase 1 trials. As many of you know this is one of my biggest areas of interest. I have advocated for years for better (more therapeutic) phase 1 trials. Through this process I have learned a ton. I now have a pretty good understanding of the issues from both sides. It is from this perspective that I have learned that while it is nice to advocate for better trials, drugs, and designs it is also important that parents really know how to deal with and interpret the options that are before them now.

Over the next few weeks I will be writing several articles on this topic. It is too complex to discuss in one simple entry. After all, I have just spent a page talking about the issues of phase 1 trials and I haven't even begun to mention their structures which are another important aspect of judging the appropriateness of their timing.

So, for a bit, you will have to put up with reading my technical dribble. The good news is that, by the end, I promise you will know exactly what to ask and how to evaluate the appropriateness of any phase 1 trial. You will be equipped to find the absolute best answer for your child in a world that seems full of a bunch of half-baked questions.

Think of it as your own personal purpose gun.