Phase 1 Trials: What to Expect

In In The News by Barbara Jacoby

By: Andrea S. Blevins Primeau, PhD, MBA


A phase 1 clinical trial is typically a first-in-human study of an experimental therapy, and its historical purpose was to evaluate the safety and identify potential side effects of that investigational treatment, as well as determine an appropriate dosage for use.1 The American Society of Clinical Oncology (ASCO) states that phase 1 trials are critical to translating basic research findings into treatments for patients.2

Many modern phase 1 trials are now including efficacy reporting of the experimental therapy — particularly response rate — as one of the endpoints.3 In addition, some phase 1 trials include a phase 2 extension trial as well, which provides preliminary information on the therapy’s efficacy.1,3

Both phase 1 and phase 2 trials are usually (but not always) required before a therapy moves to phase 3. Phase 3 is used to gather information about the therapy’s safety and efficacy in a large population in the pursuit of US Food and Drug Administration (FDA) approval.1 Some treatments receive FDA approval without a phase 3 trial.3

Most phase 1 trials are small and enroll approximately 20 to 80 patients.1 Because the efficacy and safety of the experimental therapy is typically unknown, there are important risks and benefits that patients should consider before enrolling in a phase 1 trial. In addition, many therapies that enter phase 1 trials ultimately do not receive FDA approval (the likelihood of approval for oncology drugs tested in phase 1 trials is 6.7%).4

Risks and Benefits

There are several potential risks for patients who participate in phase 1 trials. A key risk is the threat of developing an adverse event, which may or may not be permanent, and an associated danger is the risk of death attributed to the experimental therapy.5 The rates of treatment-associated deaths are low at approximately 0.5%, but it is nonetheless possible.6,7 In addition, the experimental treatment may not be effective or found to be not as effective as standard treatments.8

Patients should also be aware that phase 1 clinical trials require a commitment to an intense clinical schedule, which includes multiple visits to the clinic and may also require biopsies or other procedures.8 This commitment may also result in out-of-pocket costs for patients.9

Although Medicare and most private insurance companies often reimburse direct medical expenses associated with a clinical trial, and drug company-sponsored studies often pay for all direct medical expenses, patients are still responsible for indirect costs.10 One study estimated that the median indirect out-of-pocket cost was $985 per month, and the highest costs appeared to be carried by patients with lower incomes or who were unemployed or not working outside the home.9 Out-of-pocket costs include travel costs such as for gas or public transportation, loss of work income, and cost of child care.

The major benefit of participating in a phase 1 trial is the potential that the experimental therapy will shrink or stabilize the cancer.2 Overall, it is estimated that approximately 7% to 11% of patients experience tumor shrinkage in phase 1 trials, with up to 34% to 48% experiencing at least stabilization of their cancer.6,7 The actual response rate varies between trials. This may be particularly important to some patients, as most patients enrolled in phase 1 trials have metastatic disease that has already progressed after the receipt of other treatments.1 In addition, other potential benefits include access to new treatments and helping advance scientific research.

However, some experts caution that phase 1 trials offer little benefit to most patients, as the risks are typically more pronounced than the benefits in this early phase of experimentation.3,10 There is some debate on the ethics of phase 1 trials, and patients should be aware of all potential risks before agreeing to participate.

What to Expect

Once patients and their providers discuss and decide to pursue enrollment and select a phase 1 trial, the patient will be screened by study staff to see if their characteristics fit the eligibility criteria of the trial.5 During this process, the study staff explain the clinical trial, including what is being studied and what is required of the patient.1 Patients have the opportunity to ask questions. Patients who wish to continue with the enrollment process at this time are asked to sign a consent form, which states that the patient was informed of the potential risks and benefits of the trial, and that their questions were answered.

Patients may want to ask questions about the treatment and/or tests that are required, how the experimental therapy compared with standard treatments, the possible side effects, how long the trial may last, what the time commitment is expected to be, and who will be in charge of their medical care.

After consenting to participate, patients are screened to ensure that they fit the eligibility criteria.1 The inclusion criteria vary for different studies, but may include age, stage of disease, family history, or genetic profile, and exclusion criteria—which typically bar patients from participating based on circumstances such as the existence of prior or current health conditions other than the cancer, or the receipt of certain medications in the past.

Patients who meet the inclusion criteria will then undergo baseline testing.1 This could be laboratory testing and/or molecular testing. Then, patients will begin their assigned experimental treatment.

During treatment, patients will return to the study site for follow-up visits, where additional testing may be performed to monitor for specific side effects and, in some cases, efficacy.1,8 The study staff also evaluate the patient for any symptoms of side effects.

If a side effect develops, it will be treated according to the current standard of care and does not necessarily mean that the patient will have to stop the experimental drug or leave the trial.8 This is determined based on the type of side effect observed and its severity.

Patients can continue the experimental therapy and participate in the phase 1 trial for as long as they benefit from that treatment, with many phase 1 trials lasting about 2 years.8 If a patient’s disease progresses during the trial, they typically will discontinue the experimental therapy and either enroll in another clinical trial, switch to another treatment outside of a clinical trial setting, or elect to enter hospice.


  1. National Institutes of Health. National Institute on Aging. What are clinical trials and studies? Updated May 17, 2017. Accessed March 3, 2020.
  2. Weber JS, Levit LA, Adamson PC, et al. American Society of Clinical Oncology policy statement update: the critical role of phase I trials in cancer research and treatment. J Clin Oncol. 2015;33:278-284.
  3. Adashek  JJ, LoRusso PM, Hong DS, Kurzrock R. Phase I trials as valid therapeutic options for patients with cancer. Nat Rev Clin Oncol. 2019;16:773-778.
  4. Wong KM, Capasso A, Eckhardt SG. The changing landscape of phase I trials in oncology. Nat Rev Clin Oncol. 2016;13:106-117.
  5. Mahipal A, Nguyen D. Risks and benefits of phase 1 clinical trial participation. Cancer Control. 2014;21:193-199.
  6. Italiano A, Massard C, Bahleda R, et al. Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy. Ann Oncol. 2008;19(4):787-792.
  7. Horstmann E, McCabe MS, Grochow L, et al. Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med. 2005;352:895-904.
  8. Carter D. Q&A: Phase I clinical trials. The University of Texas MD Anderson Cancer Center. Published November 16, 2016. Accessed March 3, 2020.
  9. Huey R, George G, Philips P, et al. Out-of-pocket costs and financial toxicity experienced by patients in early-phase clinical trials. J Clin Oncol. 2019;37(suppl 15; abstr e18383).
  10. Kimmelman J. Phase I trials as therapeutic options: (usually) a betrayal of evidence-based medicine. Nat Rev Clin Oncol. 2019;16(12):719-720.