Phase 1 clinical trials, explained: 11 things to know

Phase 1 clinical trials are the foundation for how we develop new drugs to treat cancer. Typically, they involve about 60 or fewer patients and study a new medicine’s effect on several different cancer types.

Here, I’ll explain more about Phase 1 clinical trials and answer patients’ most frequently asked questions.

What is a Phase 1 clinical trial?

Phase 1 clinical trials are the first time an experimental drug is used to treat humans. It starts with researchers figuring out a pathway to treat cancer. A drug company then develops a medication that mimics that process. The primary purpose of a Phase 1 clinical trial is to figure out how much of the drug we can safely give patients and see a benefit.

Phase 1 clinical trials also help us determine which types of cancer benefit from these drugs.

How does a Phase 1 clinical trial differ from a Phase 2, 3 or 4 clinical trial?

Each phase of a clinical trial has a different goal.

Phase 1 determines the safety of a cancer drug and how much of the drug patients can tolerate. Doctors start by administering a low dose of the new drug and then increasing the dose by small increments. Unlike Phase 3 clinical trials, there’s usually not a placebo in a Phase 1 trial. Everyone gets the drug, just at different dosage levels.

Phase 2 looks at how effective and safe the drug is by seeing if a certain type of cancer responds to the treatment.

Phase 3 tests to see if the new treatment is better than the standard treatment. This is the last phase before drug approval.

Phase 4 is conducted after a drug is approved by the Food and Drug Administration (FDA) and is already on the market. Large groups of patients are monitored for side effects and to check the drug’s safety and efficacy.

Who should consider participating in a Phase 1 clinical trial?

Phase 1 clinical trials aren’t for everyone. Most patients who choose Phase 1 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 1 clinical trial.

Be sure to consider the time commitment before enrolling in a Phase 1 clinical trial. The frequency varies. For some trials, patients may need to come to the clinic every three weeks; others may need to come once a week. Keep in mind that the first 1 to 2 months can be the most time-consuming.

Who will be involved in my care during a Phase 1 clinical trial?

In a Phase 1 clinical trial at UT MD Anderson, you will interact with several members of the research team. These include:

• Principal investigator: This is the doctor responsible for the design, development and conduct of the clinical trial.
• Research nurse or study coordinator: This person helps manage the information collected in the trial and educates you about the trial.
• Clinical nurse: This nurse will coordinate your care in the clinic where you’re being treated.
• Mid-level provider: This advanced practice registered nurse or physician assistant works with your doctor and, at times, may perform clinic visits independently without the doctor.
• Business center specialist: This person will handle all matters related to billing and insurance.
• Social work counselor: At UT MD Anderson, each patient is assigned a social work counselor, who can recommend counseling services and support groups and helps you with lodging and transportation.
• Case manager navigator: This member of your team can provide you with information about home health services, nursing home and hospice services and rehabilitation services.
• Patient advocate: Your advocate can help you with any concerns that you or family members have related to your care at UT MD Anderson.

What happens during a Phase 1 clinical trial?

After you agree to participate in a Phase 1 clinical trial, you’ll take part in a process called informed consent. This is when the researcher or nurse from the trial will go over your specific trial’s purpose, procedures, risks and benefits. You’ll then be asked to sign a document stating that you understand these risks and benefits. Remember, your participation in the trial is completely voluntary, and you can choose to stop at any time.

Phase 1 clinical trials are very intensive and require multiple visits from the patient. Since it’s the first time the drug is being used in humans, we’re very careful.  It may take 1 or 2 weeks for an initial evaluation. You’ll need to be prepared to stay close to the clinic during this time. As the trial moves forward, you may be required to make frequent returns to the clinic for diagnostic testing and evaluation. It gets a bit easier once you get past the initial stages of being on the clinical trial.

How long will I be enrolled in a Phase 1 clinical trial?

You can usually stay on a Phase 1 clinical trial as long as you benefit from it. A traditional Phase 1 clinical trial lasts about two years – from the time we start enrolling to the time that we actually close out a study.

Will I have side effects?

Typical cancer treatment side effects include nausea, vomiting and diarrhea. But side effects are different for each patient in each trial.

We try to give you 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.

What happens if my condition doesn’t improve?

If your clinical condition declines, it may just be because of side effects, and we can address those issues. Or, it could be because the tumors are growing.

We get new images of 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 a patient off the clinical trial if a tumor grows a certain percentage.

What happens next depends on how you’re doing overall. Many patients go on to another Phase 1 clinical trial or back to their medical oncologist because they have one more therapy to try. Or, if the patient is out of options, they may choose to go to hospice.

What are some of the Phase 1 clinical trials we have at UT MD Anderson?

There’s a lot of exciting research happening. More than 100 Phase 1 clinical trials are being conducted at any given time.

We ran a Phase 1/2 clinical trial looking at the targeted RAS inhibitor therapy daraxonrasib, which works by blocking the pathways that promote growth in RAS mutations. In particular, mutations in the KRAS gene are present in most cases of pancreatic cancer. The success of the Phase 1/2 trial led to the Phase 3 trial, and now daraxonrasib is the new standard of care as a second line treatment for RAS-mutant pancreatic cancer. It’s doubled survival rates.

What advice do you have for caregivers of patients enrolling in Phase 1 trials?

My number one piece of advice is don’t push your loved one to do a Phase 1 clinical trial. It’s not always the best choice for them.

Second, be prepared to support them throughout the clinical trial. It’s an intensive and time-consuming process. They’ll need transportation to and from appointments as well as housing during this time.

Finally, ask questions. You need to be informed.

What should patients know about Phase 1 clinical trials at UT MD Anderson?

Patient safety is our top priority. Each Phase 1 clinical trial follows strict rules and guidelines, and must be approved and monitored by one of UT MD Anderson’s institutional review boards. The boards meet on a regular basis and include doctors, nurses, scientists, chaplains, social work counselors and patients.

We’re seeing a lot of hope in the Phase 1 environment. There’s been an explosion of new drugs in the past two decades. And there are over 1,000 new cancer drugs in the pipeline. We’re seeing a lot more activity with drugs that are actually working in many different tumor types. We’re also getting much more sophisticated in how we identify patients for clinical trials. I’m an optimist, and I’m excited about what’s ahead.

David Hong, M.D., is deputy chair of Investigational Cancer Therapeutics at UT MD Anderson.

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