Clinical Trials Provide Real Hope

Real hope is a promise for a better tomorrow. Real hope fuels my dreams. Real hope for cancer patients depends on clinical research. Research saves lives. The only way that a promising new cancer therapy can be brought to market in the United States is through the clinical trial process. Clinical trials are designed to make sure that new therapies are safe and effective.

Clinical research gives us forward thinking therapies. Yet fewer than 5% of adult cancer patients that are eligible for a clinical trial choose to enroll in one. There are many reasons for this statistic. According to a Harris Interactive Survey, 85% of patients are unaware that clinical trials are a treatment option.

When given information about clinical research, survey respondents affirmed its importance and 32% of American adults indicated they would be very willing to participate in a (cancer) clinical trial if asked. This is good news, because according to the National Cancer Institute, if only 10% of eligible adults participated in clinical trials, studies could be completed in one year, instead of the 3-5 years that studies currently require.

I believe if the clinical trial process is demystified more adults will choose to enroll.

The Phases Of Clinical Research:

Clinical research is divided into phases. Each phase has a different purpose. Let’s review these phases.

The Pre-Clinical Phase:

Before any therapy can be tested in humans Pre-Clinical research needs to be completed. In the pre-clinical phase drugs are tested to see what the drug does to the body (pharmacodynamics) and what the body does to the drug (pharmacokinetics). The potential therapy is also tested to see how it is absorbed, distributed, metabolized and excreted by the body. Toxicity is also studied. Pre-clinical testing is done both in test-tubes/petri dishes (in vitro) and in living organisms such as mice (in vivo).  Information collected from pre-clinical studies guides how researchers proceed to design a safe human testing protocol. Preclinical research often takes years before data from this stage can be turned into a potential new treatment introduced to humans. Researchers identify a promising compound through a scientific discovery process and test their hypothesis in pre-clinical phases before in-human studies are initiated. Potential new therapies are NOT haphazardly tested in humans. Participants in clinical trials are not guinea pigs.

Phase I Trials:

Once researchers discover a compound that is safe and effective in animals, human testing begins. Phase I trials are first in human trials. These trials usual involve only 10 to 30 people. The purpose of a Phase I trial is to determine the maximum tolerated dose (MTD), and the best way to administer the therapy. To determine the MTD the first people in the trial get a small dose of the drug and are closely monitored for side effects. If the side effects are manageable, the dose is slightly increased and monitored. Researchers keep increasing the dose until they find the highest dose that has a manageable side effects profile.

Sometimes researchers use a Phase I trial to determine the best way to administer a new compound, this could be by IV or oral. Although there is evidence that the therapy works in preclinical studies before being tested in humans, Phase I trials do not measure the effectiveness of a potential new therapy. The goal in this phase is to examine what the drug does to the body and what the body does with the drug. Phase I trials are designed to show that people can safely use a new treatment. If a participant’s cancer markers increase while on the trial or if the side effects are too severe the participant leaves the trial and a different treatment option is pursued.

Phase II Trials:

Trials in this phase are designed to test if the new treatment is effective (efficacious) and to gain more data on the treatment’s safety and side effects profile. Phase II trials can either be a single arm or have more than one arm. An arm of a clinical trial is a group of patients receiving a specific treatment.  In a single arm Phase II trial all participants will receive the therapy being investigated. Single arm Phase II trials usually involve between 30 to 120 people.

Sometimes Phase II clinical trials will have more than one arm. Some of these trials may assign different people to several possible treatments. In other Phase II trials people may be assigned to receive different doses of the same treatment. Researchers call this a randomized Phase II trial. Such a trial may have up to several hundred patients

Researchers will test the effectiveness of the therapy in a Phase II trial in different ways depending on the goal of the treatment.  Efficacy can be examined by measuring tumor shrinkage or blood markers depending on the cancer. Other trials may measure if the new treatment keeps the cancer from getting worse (progression free survival) or improves quality of life. Most drugs that fail testing do so during Phase II. It is important to remember that if your cancer is progressing while on a trial, you are dropped from the trial and a new treatment option is sought.

Phase III Trials:

If a therapy is shown to be effective and the side effects are able to be managed during Phase II testing, the therapy will then proceed to a Phase III trial. The goal of Phase III trials is to show that the new therapy is better than the standard of care and/or has fewer side effects. The therapies that go to Phase III have shown to be effective in the Phase II testing.

Phase III trials are randomized.  Participants will either receive the standard of care or the new treatment. Participants do NOT have a choice as to what treatment arm they will be in. Often these trials are also blinded. This means that the trial participant and doctors do not know which arm you have been assigned. Phase III trials are usually multi-center and involve 300 – 3000 participants. Ideally the participants should vary in age, ethnicity and gender.

It’s important to understand that in a randomized cancer trial, placebos are usually not a trial arm. The only time a placebo will be given alone to a participant is if there is no known effective treatment. Just like in Phase I and II trials, participants are monitored closely for side effects and disease progression. The trial is stopped and a new treatment pursued if side effects are too great or if the cancer grows.

If the Phase III data shows that the new treatment works well against a specific cancer than the researchers can apply for FDA approval. FDA approval may take some time although some break-through therapies can be fast-tracked.  While trial participants are awaiting FDA approval they usually continue to receive the possibly lifesaving drugs until the drug can be obtained on the market.

Phase IV Trials:

Phase IV trials occur after a therapy has been FDA approved. Phase IV trials look for safety over time.  Drugs that are being studied in Phase IV trials are available for doctors to prescribe to patients even if they are not on a trial. Phase IV trials may answer questions about late term side-effects and overall survival.

Clinical trials provide hope. Next time you have a treatment decision to make consider participating in a clinical trial. You may gain access to promising new treatments and get expert care, but before you sign the informed consent form make sure you know what phase the trial is in, the purpose of the trial and the possible risks and benefits of participating. Let’s keep our dreams alive.

Cindy Chmielewski Precision Medicine Advocate

Cindy Chmielewski Precision Medicine Advocate

Cynthia Chmielewski was diagnosed with multiple myeloma, a blood cancer, in 2008. Cindy’s induction therapy stopped working after a few cycles and she proceeded with a stem cell transplant which failed to put her into remission. Depressed and scared she continued her fight using newly FDA-approved targeted therapies which eventually put her in remission. Cynthia continues treatment with a maintenance protocol.  Cynthia is using her passion for education to teach a new group of “students” – myeloma patients, their caregivers and others interested in myeloma.  She is a trained mentor, advocate and Patient Ambassador.