In 2022, there were an estimated 20 million new cancer cases and 9.7 million cancer-related deaths, according to the World Health Organization. About 1 in 5 people develop cancer in their lifetime, with approximately 1 in 9 men and 1 in 12 women dying from the disease worldwide, highlighting the urgent need for innovative treatments.

In the quest for groundbreaking treatments, phase 1 oncology trials hold great promise for patients battling cancer. These trials represent the crucial first step in evaluating the safety and efficacy of potential therapies in humans.

Phase 1 oncology trials unveil a world of intricate study designs, patient considerations, and emerging trends that collectively shape the landscape of cancer treatment.

The significance of phase 1 oncology trials

Oncology drug trials are amongst the most popular studies conducted globally, accounting for 23.1% of all trials in 2020, and increasing at a rate of 6.5% per annum, compared to 3.6% for non-oncology drugs. Phase 1 oncology trials, in particular, form a critical foundation for future cancer treatments. Unlike later phase trials focusing on efficacy, phase 1 trials primarily aim to establish the safety profile of investigational drugs and determine the maximum tolerated dose (MTD). They also provide invaluable insights into the pharmacokinetics and pharmacodynamics of experimental drugs, laying the groundwork for subsequent clinical development stages. In contrast to most other therapeutic areas, phase 1 oncology trials are conducted in small patient cohorts instead of healthy volunteers, often comprising individuals who have exhausted standard treatment options, offering them a ray of hope in their battle against cancer.

Phase 1 oncology study design

Central to phase 1 oncology trials is their distinctive study design tailored to the unique challenges posed by early-phase research. Traditionally, the 3+3 design has been a cornerstone in dose escalation methodologies, where cohorts of three patients are sequentially enrolled at escalating dose levels until dose-limiting toxicities (DLTs) are observed. However, novel designs such as adaptive dose escalation and Bayesian methods are gaining traction, offering more efficient dose-finding strategies and faster pathways through early product development.

Adaptive dose escalation methods are designed to be flexible and responsive, adjusting dose levels in real-time based on patient responses and observed toxicities. This adjustment allows for more individualized dosing, minimizing the number of patients exposed to subtherapeutic or excessive doses. By continuously monitoring patient responses, these methods improve safety and efficiency, often requiring fewer patients and shorter trial durations to identify the MTD compared to traditional designs.

Bayesian dose escalation incorporates prior knowledge and ongoing patient data to continuously update the probability of different dose levels being safe and effective. Bayesian models use a probability-based framework to calculate the likelihood of each dose level being the MTD, allowing for a more nuanced understanding of dose-response relationships. As new patient data is collected, these models are updated to refine dose estimations, improving decision-making in real-time.

Patient considerations and informed consent

Upholding ethical principles and prioritizing patient welfare are fundamental tenets guiding the conduct of phase 1 oncology trials. Given the experimental nature of these studies and the inherent risks involved, clear communication with participants regarding potential benefits, risks, and uncertainties is essential. Adequate information, support and resources are also key to clinical trial participation. Sponsors and CROs should work closely with sites to ensure participants have access to comprehensive information to obtain their informed consent, and that trial requirements are not too onerous. For example, allowing for remote assessments in the trial design, such as for interim and follow-up visits, can create a less tiring schedule for sick patients.

Challenges and opportunities in phase 1 oncology trials

While oncology trials hold immense promise, they are not without challenges. Patient recruitment, particularly for rare cancer types or specific genetic subtypes, can be a formidable hurdle. Moreover, ensuring compliance with rigorous safety protocols and stepwise decision-making both demand meticulous planning and expertise. However, amidst these challenges lie opportunities for innovation and progress. The advent of combination therapies, immunotherapy, and targeted agents has revolutionized cancer treatment paradigms, offering new avenues for personalized and precision medicine. Trends, such as basket and umbrella trials, which evaluate multiple drugs or drug combinations across different cancer types or molecular alterations, showcase the potential of a more holistic approach to cancer therapeutics.

Looking ahead, the phase 1 oncology landscape will continue to evolve; innovative trial designs, harnessing advanced statistical methodologies, and predictive modeling hold promise for more efficient dose escalation and patient selection strategies. Furthermore, integrating biomarkers and molecular profiling technologies enables a deeper understanding of tumor biology, paving the way for personalized treatment approaches.

Phase 1 oncology trials represent the nexus of scientific innovation, patient empowerment, and hope in the fight against cancer. Through rigorous study designs, ethical conduct, and collaborative endeavors, these trials offer promise for transformative advancements in cancer care.

If you want to learn more about how you can successfully navigate clinical research in Australia with a team of professionals committed to safe and ethical studies, get in touch with us today.

Southern Star Research is a full-service Australian Contract Research Organization. We help sponsors run safe and efficient trials that meet regulatory requirements, ensure scientific excellence, and demonstrate the commercial viability of your product. If you're looking for an agile and dedicated team to help you run a successful trial, contact us today.