Understanding Early Phase Oncology Trials
Early-phase oncology trials are the first stages in testing new cancer treatments. This usually encompasses phase I and phase II of the three main oncology clinical trial phases, where patients are among the first to test a new treatment. As our understanding of cancer has progressed over the last decades, the methodology of early-phase oncology trials has also become much more sophisticated in recent years.
As a result, modern approaches to early-phase oncology trials take into account areas that were less considered in the past, such as proof-of-concept definition, optimisation of timelines, early KOL involvement, and competitive asset positioning.
This article discusses the stages of early-phase oncology research and key considerations associated with early-phase oncology clinical trials.
Phase I
Phase I is the first step in testing a new treatment in humans, usually involving 20 to 50 volunteers. The main aim is to assess the treatment’s overall safety and identify a suitable dosage range. This stage often marks the treatment’s first use in people and is carefully designed to minimise risk.
Volunteers receive the treatment in small groups, starting with a low dose. Researchers monitor each group closely before increasing the dose for the next group, a method known as dose escalation. This helps identify the highest dose that can be given safely without serious side effects.
Although the number of participants is small, phase I oncology trials can take time, as each step is carefully reviewed. If results show the treatment is generally safe, it can move on to phase II. Around 70% of treatments successfully progress past this stage.
Phase II
Once a treatment is shown to be generally safe in phase I, it moves into phase II. Here, the focus shifts to testing how well the treatment works, while still monitoring safety.
This phase involves a larger group, sometimes over 100 patients, who actually have the condition. Researchers measure specific effects, such as slowing disease progression or easing symptoms, to see if the treatment is doing what it’s designed to do.
Trials in this phase often last several months, and some are randomised to remove bias and improve reliability. Side effects that didn’t appear in phase I may also emerge here due to the bigger sample size and longer timeframe. About 33% of treatments move beyond phase II, as the testing becomes more rigorous and revealing.
Later Phase Trials
Later trials, however, focus more on comparing new treatments to the best available care and on real-world safety. Phase III (phase 3) studies are large, usually randomised trials, often involving many hospitals and sometimes thousands of patients. They aim to determine which treatment works better for a specific cancer, investigate side effects and quality of life, and test variations like new drugs, different doses, schedules, or delivery methods. Phase IV (phase 4) studies happen after a drug is licensed and look for rarer side effects, long-term risks and benefits, and how well the treatment performs when used widely outside the controlled setting of earlier trials.
Key Considerations
The evolution of early-phase oncology trials
Cancer is now commonly understood as many types and molecular subtypes of disease. It is an increasingly segmented therapeutic area, requiring complex, agile study designs to meet persistent unmet medical needs and driving advances in early clinical development oncology.
Operating beyond the traditional scope of general toxicity, safety, and efficacy, early-phase cancer trials require more advanced and tailored methods of research, namely, investigating molecular, genomic, and biomarker-driven principles. Agile approaches to such translational medicine can make oncology clinical trials different from other therapeutic areas.
Patient considerations
Early phases of clinical research are a challenging step in the clinical development of any drug. In rare disease and oncology, there can be additional challenges in patient recruitment due to the small size of molecularly defined population subsets.
The sample size can become even smaller when the study requires patients with matching specific genomic types of cancer, which is often one of the key issues surrounding the development of new chemotherapy drugs.
As a result, it is crucial to consider the role of the patient in early-phase oncology trials, integrating effective patient engagement strategies into the study design. Doing so can help avoid the risk of dropout and reduced sample sizes during later stages.
Regulatory and ethical considerations
Studies that evaluate patient understanding of their involvement in clinical research find that 30% of patients do not understand that they may not directly benefit from taking part in a given clinical trial. This highlights the ethical need to ensure that patients are fully informed about the potential risks and benefits of taking part in clinical research.
Not only does this require regulatory procedures and documentation, but there is also a responsibility for researchers to ensure that the patient is fully informed and given the opportunity to ask questions about the trial.
This is particularly important in oncology research as many patients with advanced cancer may consider a clinical trial as their only remaining treatment option.
Full-service CRO
Simbec-Orion is a full-service, agile early phase oncology CRO delivering end-to-end clinical development solutions in oncology and rare diseases. Our expertise spans clinical pharmacology and trial management, covering everything from patient recruitment, protocol design, and trial delivery to data processing and regulatory support. We design and deliver customised programmes tailored to your needs, acting as an extension of your team to manage complex studies reliably. With almost 50 years of CRO experience partnering with clients worldwide, we offer flexible support for early-phase pharmacology through large multicentre trials. To learn more about early phase oncology studies, watch our webinar here, or get in touch via the contact form to find out how we can help.