The clinical trial landscape is constantly evolving, particularly in oncology early development, influenced by shifts in regulatory guidance such as the US Food and Drug Administration’s Project Optimus initiative or its draft guidance on Multiregional Clinical Trials in Oncology. This new era requires a solid understanding of the requirements and potential challenges, along with a strong command of the solutions needed to mitigate risks and optimise trial outcomes.
Below are suggested strategies to ensure success in operationalising global early-phase oncology trials.
Managing Dose Optimisation and Complex Study Designs
Project Optimus emphasises dose optimisation in early-phase oncology trials should not be based solely on maximum tolerated dose (MTD) but should include pharmacokinetic (PK) and pharmacodynamic (PD) data, resulting in complex study designs that necessitate larger sample sizes and a broader global footprint. Sponsors and contract research organisations (CROs) must balance robust data collection with the practicalities of patient recruitment and retention across diverse regions and regulatory environments.
Tackling Operational Execution on a Global Scale
Operational execution in early-phase trials involves coordinating numerous factors during study startup and trial planning. A strong understanding of regulatory requirements and compliance with local laws is crucial for smooth trial initiation and progression. Knowledge of regional data privacy regulations safeguards patient information and maintains trust.
Enrollment and cohort management can be challenging in global trials with multiple sites located across various regions and time zones. Global study teams must be proficient in protocol knowledge, including managing multiple treatment arms, varying doses, and adaptive trial designs.
Sites must be adequately staffed and equipped to handle cohort specific needs, requiring coordination of specialised personnel, medical equipment, and materials. Adding to the complexity of early-phase trials is risk-based monitoring, safety review, vendor management, investigational product (IP), and sample management. Effective communication and coordination among the various stakeholders are essential to trial success.
Planning for Trial Success, Adapting to Changes
Mapping out the clinical study plan from the beginning is vital, especially for small biotechs. Capitalising on a CRO’s knowledge and experiences can be beneficial. Risk mitigation methods, including planning for unexpected events such as natural disasters and geopolitical climates, are essential in early planning.
Leveraging automated document management tools can reduce administrative burdens and speed study startup. Likewise, master service agreements can fast-track site contract negotiations and have a positive impact on global startup timelines.
Changes are inevitable in early-phase oncology trials, so remaining adaptable is key. Amendments to study protocols are frequent, so having a flexible setup process that allows for adjustments is crucial. For example, a trial may start as a first-in-human trial in one country and expand globally over time. Careful advanced planning helps anticipate amendments and effectively manage transitions and predict trial milestones.
