About Clinical Trials and My Experience so Far

This is a long post about clinical trials and my experience so far.  Not for everyone.

What is a clinical trial?  A clinical trial is a research study done after previous research (typically in animals) has shown that a new compound or treatment may be beneficial to patients.  Trials are typically funded and managed by the company or institution that created the treatment; however, in some cases the government will fund a study through, for example, the National Institute of Health (NIH).  The NIH describes clinical trials this way:

·      Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

·      Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

·      Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

·      Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

I think a Phase I trial may be the most dangerous and unpleasant of the trials because before the trial, the researchers do not really know how people will respond to the treatment.  Part of the trial is a dose escalation phase in which the maximum tolerable dose is determined.  Patients are given increasingly stronger doses until they develop serious side effects or quit the trial because of the side effects.  My clinical trial is an expansion of Phase I.  The drug GDC-0919 has been given to a small number of patients and the effects of different dose levels have been examined.  The expansion adds additional patients with different cancers and different characteristics.  I think it may be unusual, but my trial is being conducted at 11 sites in the US and is being set up in three sites each in France, Korea, and Spain.  It suggests to me that they think they are on to something good with GDC-0919.

A Phase I trial also provides some evidence of effectiveness; however, more patients with perhaps different diseases are needed to get sufficient evidence of success, the Phase II trial. 

The Phase III trial is where the rubber meets the road.  In this phase, the new treatment is compared with a previously approved drug or treatment to measure effectiveness and safety.  I think Phase III trials are often done in multiple locations in order to get more and a better variety of patients.  If the Phase III trial shows that the treatment is effective, the sponsor determines whether or not to seek approval from the Food and Drug Administration (in the US).

How does one find clinical trials?  A clinical trial may be suggested by your doctor, or you can go online and search for them.  The best source of trials can be found on the NIH website: https://clinicaltrials.gov/.  You can search by disease and trial location.  If you look at the entry for my trial (https://clinicaltrials.gov/ct2/show/NCT02471846?term=gdc-0919&rank=1) you will see:

·      the purposes of the study,

·      a description of the various arms (groups of patients) of the study,

·      the requirements for participation in the study,

·      the conditions for elimination for the study, and

·      information about where the study is being conducted.

If you live near a NCI designated Comprehensive Cancer Center, you can probably find a list of locally available trials on their web site.

How to join a trial.  When I applied for a clinical trial run by the NCI last January, I think I applied before talking to my oncologist about it; however, I think it would be a good idea to talk to your doctor first.  You first contact the study coordinator and complete their paperwork.  I had to have the hospital send certain medical records to the NCI.  For the trial here in Denver the hospital already had the medical records on hand.

The medical records are used to determine if you are sick enough but not too sick to participate in the trial.  They look at the list of inclusion criteria to ensure that you are sick enough.  For example, in my case, I had to have solid tumors, and they had to show “Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care.”  The idea being that they do not want to use an experimental drug that might be unsuccessful when an already approved standard treatment is available. 

They also want to make sure that participants do not have other conditions that might keep them from completing the trial.  The NCI rejected my application because I use supplemental oxygen; i.e. I was too sick to participate.  I asked my oncologist to let them know that I lived in mile-high Denver and had not used oxygen the summer before when traveling from Denver to Michigan and back.  Bethesda, MD is near sea level, so I would be OK.  They accepted his argument, and I was accepted; however, congestive heart failure arose, and I withdrew from the trial. 

The prescreening.  For my trial, I had to have a prescreening visit in which I was weighed, measured, and poked.  I also had to have a tumor biopsy because my tumor cells had to display the PD-L1 protein.  That involved inserting a coring needle through my back into my tumor and extracting a piece of the tumor.  The procedure was done as a day-surgery, and I was given some anesthesia during the process.  Of course, you have to go through a consent form with the provider to ensure that you know what will be happening and what the risks are.  My consent form was eight pages long, but it was clear and the nurse practitioner made sure we talked about all aspects of the form.

Starting the Trial.  A week before my first treatment, I had another exam, many tubes of blood drawn, and a CT of my lungs.  Genentec, the company sponsoring the trial, covers the bases thoroughly.  Eighteen blood tests were run on the blood drawn that day.  The consent form was 37 pages long, but the nurse practitioner went over it page by page to make sure everything was clear.  To participate, you basically give your body to them.  I agreed . . .

·      that I would receive no compensation for participation,

·      that they can take the tissue as described in the consent form,

·      that they can keep what is in excess for other research purposes, and

·      that I understood that the risks of the treatment are not fully understood because it is experimental. 

They agreed . . .

·      that I can withdraw from the program at any time,

·      that they will bear the costs of the study including treatment for harm done by the treatment,

·      that I am responsible for any costs that would be part of my regular medical treatment, and

·      that they will protect my privacy.

The study is run in three-week cycles, and the consent form went through what would be done in each cycle—blood draws, infusions, CTs, biopsies, etc.

For Genentec this is more than a study of how effective these two drugs, Tecentriq and GDC-0919, are when given together and how they might interact.  The tissue and blood samples will contribute to their ongoing research about how cancer forms and spreads.  They may sequence my entire genome for their research purposes, and neither I nor my doctor will have access to the results.  They may make tons of money from the combined data of the participants.  I’m OK with that because my cells and molecules might contribute to the advancement of science and medicine.  I’m happy to contribute in honor of the clinical trial participants who paid it forward in getting us to the state we are in now with cancer treatment.

One week later, October 27, when all that information had be examined, I went to the hospital for my first treatment.  More routine blood draws and a urinalysis were performed, and when the results didn’t find any problems, I went down to the infusion center to get my first dose of Tecentriq.  The infusion took 30 minutes, and I had to wait under observation for 30 more minutes with a blood draw before the infusion and after the observation period.  Nothing happened to be observed.

Blood is taken at different times in a trial cycle for three purposes.  General blood tests and a urinalysis are taken before any office visit to see if my general health is strong enough to continue.  At an infusion of Tecentriq or the initiation of a new round of GDC-0910, they take pharmacokinetic blood samples to see how long the drug remains in my body and pharmacodynamic (PD) samples to see how the body processes the drug at the same time.

I had a long day at the hospital when I returned almost three weeks later for a Tecentriq infusion and my first dose of GDC-0919.  I had a blood draw at 7:10 am, a visit with my oncologist at 8:15 am, and then went down to the infusion center.  I finally left the hospital about 5:45 pm.  They took blood before and after my infusion.  After taking my first dose of GDC-0919 they took blood at 15 minutes, 30 minutes, 1, 2, 4, 6, and 8 hours after dosing.  About a cup of blood is taken in total on these long days.  When I go back tomorrow for the start of my second cycle of the oral drug, I’ll have another long day, but that is the last one.  After that the blood draws will only be taken before treatment.

I have a port implanted under the skin of my chest which is connected by a tube to a large blood vessel, the superior vena cava.  It is accessed (virtually painlessly) when I go the lab at the start of a day.  I am left accessed which means that a sort of pigtail of tubing comes from the port needle and is used throughout the day to take blood.  The needle is removed at the end of the day (painlessly).  I love my port; however, when I get an infusion they cannot draw blood from the port because of concern that all the drug would not be flushed out and would contaminate the blood draw.  On those days, I get an IV for the infusion, and all of the blood draws are taken from the port.

So what do I do on those long days?  Once they get through the first few blood draws, I am moved from the infusion chair to a room with recliners where subsequent blood draws are taken.  I can leave and go downstairs to eat, walk around, etc. as long as I am back in the room for my next scheduled blood draw.  Last week I read a book, a magazine, and the news on the internet and played Spider Solitaire.  By the way, the people in the infusion center are great—friendly, helpful, smart, knowledgeable, efficient, and on top of things.  I am always inspired by the competence of the people at the University of Colorado Hospital.