Phase 1 Clinical Trials Are an Essential Step in Advancing the Development of New Cancer Therapies

The center's Phase 1 Clinic Trials program was established 15 years ago. It supports and streamlines the initial in-human testing required to advance new cancer treatments. 

“We see the benefits of this work in patients who respond to therapy,” says John Thompson, MD, who leads the highly successful program. “We’ve also been part of the earliest phase 1 studies of revolutionary new therapies, such as immune checkpoint inhibitors, which are now a new standard of care.”

The clinical trial research pipeline

New cancer treatments come from a variety of sources. Many emerge out of basic research investigating disease processes, cellular mechanisms and how cells interact. Fred Hutch is a leader in translational research, but pharmaceutical companies and other institutions also bring new agents forward. Sometimes, new treatments involve different drug regimens or combinations of existing drugs.

Clinical trials typically have a sponsor, such as a pharmaceutical company, to champion the process and secure FDA approval. The phases of clinical trial development include:

Preclinical development

Preclinical development occurs before the initiation of human clinical trials. It involves lab experiments and animal studies to give preliminary information on efficacy and safety. 

Phase 1 trials

Phase 1 trials are the first in-human tests of new agents. Participants typically include eligible patients who do not respond to available therapies or have a type of cancer that doesn’t have an accepted therapy. 

“Preclinical tests give us an idea of how the agent works,” says Dr. Thompson. “But often, we don’t know how the agent will work or behave in a patient.”

Groups of patients receive increasing doses of the test drug, starting with the lowest amount. The researchers assess the drug’s:

• Pharmacodynamics (how the drug acts on the body) 
• Pharmacokinetics (how the body metabolizes and excretes the drug)
• Safety

By systematically raising the dose, the researchers identify the highest level that is safe to give. This is also called the recommended phase 2 dose (RP2D).

Phase 2 trials

Phase 2 trials test how well a new agent works. All patients typically receive the same dose, though some trials use different dosing levels or regimens. Measured patient outcomes may include:

• Cancer progression
• Change in tumor size
• Lifespan
• Quality of life

“We frequently combine phase 1 and 2 trials,” says Dr. Thompson. “Operationally, a phase 1/2 trial makes sense, since the research team is familiar with the drug, the side effects and how to manage the drug in patients.”

Phase 3 trials

Phase 3 trials compare the new agent to the standard of care. These trials randomly assign participants to treatment groups. Test therapies that outperform standard treatments typically become FDA approved and the new standard of care. 

Managing the complexities of phase 1 clinical trials

Phase 1 trials require a large team of experts, including physician investigators who specialize in specific disease groups. Each trial may include multiple investigators with different areas of expertise. 

Along with physician investigators, research coordinators, data coordinators and nurses also manage clinical aspects of the trial and ensure accurate data collection. The team also includes regulatory affairs staff and financial coordinators.

Some important clinical aspects of phase 1 trials include:

Selecting a target 

Phase 1 trials may span multiple cancer types, since researchers may not fully know the best disease site for drug activity. 

“Based on our understanding of the agent’s mechanism of action, we may be able to make an informed opinion about where the drug would be most successful,” says Dr. Thompson. “For targeted therapy and immunotherapy agents, molecular testing also helps us develop a more targeted approach.”

Some phase 1 studies may be open to all patients who have a particular gene mutation. That means eligibility may be based more on the molecular traits of a particular cancer than its location. 

Recruiting patients

Participation in phase 1 trials is voluntary. Research coordinators and Phase 1 team physicians meet with patients to explain the trial and what to expect. If they are interested in participation, they sign an informed consent document. Next, patients undergo a detailed screening process to determine eligibility. 

Managing patients

Administering test drugs and managing patients requires a high level of skill and coordination. Research coordinators work with nurses who are experts in administering phase 1 drugs to cancer patients.

After administration of the test drug, nurses perform pharmacokinetic tests, which involve drawing timed samples of blood or body fluids. Often, these samples must be processed quickly and precisely. The team also evaluates drug safety through physical evaluations and blood tests while providing ongoing monitoring for side effects. 

Analyzing data 

Data coordinators collect and analyze results from the different dose levels and decide whether to recommend the RP2D for a phase 2 trial.

“Phase 1 trials often occur simultaneously at multiple institutions,” says Dr. Thompson. “We use paperless reporting forms and shared data systems to ensure consistent reporting.”

Referring a patient to Fred Hutch for a phase 1 trial

The availability of Phase 1 trials changes quickly. Program staff compile a list of current trials every other week broken down by disease type. Physicians interested in information about open trials can contact the program at phase1pc@seattlecca.org to sign up to receive this list via email. 

Fred Hutch Phase 1 Program specialists work closely with patients and community oncologists. Dr. Thompson welcomes inquiries about the program. “Often we have more than one trial that might meet a patient’s needs,” he says.