A new treatment goes through several phases. Each phase has a different purpose:
- Phase I trials test if a new treatment is safe and look for the best way to give the treatment. Doctors also look for signs that cancer responds to the new treatment.
- Phase II trials test if one type of cancer responds to the new treatment.
- Phase III trials test if a new treatment is better than a standard treatment.
- Phase IV trials find more information about long-term benefits and side effects.
Most of the time, when you take part in a clinical trial, you will only be in that one phase of the study. Treatments move through the phases, but patients do not.
Phase I Trials
Test if a new treatment is safe in people. Doctors also find the best way to give the treatment.
The goal of a Phase I trial is to:
- Find out if a new treatment is safe.
- Find the best way to give the new treatment, such as by mouth or by vein.
- See if there are signs that cancer responds to the new treatment.
Phase I trials usually include 15 to 30 patients who are divided into small groups. These groups are called cohorts. The first cohort receives a dose of the new drug. Doctors may collect blood or urine samples to measure drug levels in the patients.
If the first cohort does not have any severe side effects, then a new cohort receives a higher dose of the same drug. The dose increases with each new cohort until the doctors find the best dose for future testing. With each increasing dose, doctors test each patient to see if he or she is responding to the treatment. If the doctors find that the treatment is safe, then it will move forward to be studied in a Phase II trial.
The Clinical Center for Targeted Therapy provides many of MD Anderson’s Phase I clinical trials. Ask your doctor if you would like to learn more about this center.
Phase I clinical trials are the foundation for how we develop new cancer drugs. Typically, they involve only several dozen patients and study a new medicine’s effect on a variety of cancer types.
David S. Hong, M.D., sat down with us to explain more about Phase I clinical trials and answer some of patients’ most frequently asked questions.
What is a Phase I clinical trial?
Phase I clinical trials are the first time human beings are being treated with an experimental drug. It starts with researchers figuring out a pathway to kill cancer. A drug company then develops a medication that mimics that process. The primary purpose of a Phase I is to figure out how much of the drug we can safely give patients and see a benefit.
But that’s not the only purpose. Phase I trials also help us figure out which cancers benefit from these drugs.
Who should consider participating in a Phase I clinical trial?
Phase I clinical trials aren’t for everyone. Most patients who choose Phase I clinical trials are running out of options. Typically, they have metastatic disease, haven’t had success with standard chemotherapy, have mild or no symptoms and don’t want to go to hospice. They’re willing to see if they can help others, and possibly themselves, by participating in a Phase I clinical trial.
What questions do you hear most from patients considering Phase I clinical trials?
“Is there a placebo?” Unlike Phase III clinical trials, there’s usually not a placebo in a Phase I trial. Everyone gets the drug, just at different dose levels.
There are also a lot of questions about schedules. Phase I clinical trials are very intensive and require multiple visits from the patient. Since it’s the first time this drug has been used in human beings, we’re very vigilant.
We also get a lot of questions about side effects. Typical side effects include nausea, vomiting and diarrhea. But side effects are different for each patient in each trial. We try to give patients an overview of the most common side effects, those that are most concerning and then all possible side effects. Most side effects are reversible and treatable. We either stop the drug or we give another medication to address the side effects.
How long will a patient be enrolled in a Phase I clinical trial?
Patients can usually stay on a Phase I clinical trial as long as they benefit. A traditional Phase I clinical trial lasts about two years (from the time we start enrolling to the time that we actually close out a study).
What happens if a patient’s condition doesn’t improve?
If a patient’s clinical condition declines, it may just be because of side effects and we can address those issues. Or, it’s because the tumors are growing. We re-image patients on a regular basis, and we do measurements on the patient following a preset criteria. Depending on the drug and the set criteria, we’ll take the patient off the study if a tumor grows a certain percentage. What happens next depends on how the patient is doing overall. Many patients go on to another Phase I study or back to their medical oncologist because he or she has one more therapy to try. Or, if they are out of options, they may decide to go to hospice.
What are some of the most promising Phase I clinical trials we have at MD Anderson right now?
There’s lots of exciting research happening. In a Phase I trial of the drug LOXO-101, we’ve seen tumors shrink in patients with cancers that are linked to the gene fusion of NTRK. We’ve also seen promising results in a Phase I trial of a combination of inhibitor drugs that target a cancer cell’s signaling. Lastly, we have many immunotherapy Phase I clinical trials, but one that’s exciting is the upcoming MAGE-A10 study on the use of engineered cells of the immune system (called CAR-T cell and T-cell receptor therapies).
What advice do you have for caregivers of patients enrolling in Phase I trials?
My number one piece of advice is don’t push your loved one to do a Phase I. It’s not always the best choice for the patient.
Two, be prepared to support this patient timewise. It’s an intensive and time-consuming process.
Three, ask questions. You need to be informed.
Anything else you want patients to know about Phase I clinical trials?
What we’re seeing in the Phase I environment is a lot of hope. Within the past decade, there’s been an explosion of new drugs. There are over a thousand new cancer drugs in the pipeline. We’re seeing a lot more activity than before; drugs that are actually working in lots of different tumors types than before. We’re also getting much more sophisticated in how we identify patients. I’m an optimist, and I wouldn’t be in this field if I wasn’t.
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Phase II Trials
Test if a new treatment works in one type of cancer.
Fewer than 100 patients usually join a Phase II trial. Even though the main goal is to see if the treatment works, doctors still closely watch patients’ side effects. If the new treatment works, doctors may go on to study it in a Phase III trial.
Phase III Trials
Test if a new treatment is better than standard treatment.
Phase III trials may include hundreds to thousands of patients around the country or world. Each patient enrolled in a Phase III clinical trial has a chance of being in one of the following groups:
- Control group – the group that gets the standard treatment
- Study group – the group that gets the new treatment being tested
Doctors do not know if the new treatment is better than the standard treatment, but they believe it is as good and may be better.
After the Phase III trial, the FDA reviews the clinical trial results to make sure the treatment is safe and effective for people to use. The FDA decides whether to approve the treatment so that it is available for all patients.
There are many frequently asked questions about Phase III trials. These include:
How are patients put into groups?
A computer decides which patients are in the control group and which patients are in the study group. Patients have a chance of being in either group. The patient and doctor do not decide. It is random and due to chance alone. This helps to avoid bias in the clinical trial. (Bias happens when human choices affect a study’s results.)
Would my doctor know which group I am in?
In single blind studies, patients do not know whether they are in the control or study group, but the doctor does. In double blind studies, neither the patients nor the doctors know which patients are in each group. (In case of an emergency, doctors can find this information in the study file.)
Would I be given a placebo?
A placebo is something that looks like medicine, but is not. If a placebo is used, it is given together with the best standard treatment. This allows doctors to compare standard treatment alone to standard treatment with a new drug. If there isn’t a standard treatment, then the placebo may be given alone, but this is not common in cancer trials.
Phase IV Trials
Find more information about long-term side effects.
In Phase IV trials, doctors study treatments that the FDA has already approved. The goal of Phase IV trials is to continue studying side effects of a new treatment.
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