Oncology dose-escalation trials are a distinct entity, with nuances and considerations which set them apart from other therapeutic areas. From varying trial designs to the patients who participate, dose-finding clinical trials in oncology are a clinical research paradigm. Understanding strategies to facilitate success is key to study planning and execution, from feasibility to site selection through enrollment and treatment.
Phase I clinical trials are a critical step in the development of cancer-targeted therapies. Oncology dose escalation trials typically recruit patients who have exhausted all other potential options for treatment.
The goal of this phase of clinical trial is to establish a recommended dose and/or dosing schedule of a new therapy, either as monotherapy or in combination. Central to this is the goal of minimizing participant risk and identifying recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) with a minimum of time and participant number. With this in mind, it is important to understand the factors that drive the successful and speedy completion of a dose escalation while ensuring patient safety and rapid determination of RP2D/MTD.
Early phase oncology trials are driven by an array of factors, with patient availability a single component. Duration and success of an oncology dose escalation trial are typically driven by:
- Design (3+3, accelerated titration, etc.)
- Escalation/de-escalation parameters
- Dose limiting toxicity (DLT) evaluation period
- Time allocated for data-safety monitoring board (DSMB) cohort safety review
- Site selection, with emphasis on investigator experience, commitment, and availability of potential patients
- Cohort management across centers to ensure slots are filled as quickly as possible
Failure to address any of the above factors can put timely completion of a dose escalation at risk with potentially detrimental impacts on both participants and the development process of a potentially promising therapy.
More recently, trial design considerations have been impacted by the advent of targeted therapies and immune-oncology agents where optimization of biologic activity may not correlate with conventional dose-escalation strategies. In these situations, it is critical for sponsors to partner with a CRO well versed in oncologic therapeutics to ensure success.
Thoughtful selection of a CRO that is engaged in the evolving oncology landscape will help a sponsor to efficiently navigate the pathway of a successful dose-finding trial as the first step in successful asset development.
Michael Pace, Ph.D., Associate Director, Global Feasibility, has more than 8 years of experience within the academic and clinical research sectors, with an exclusive focus on global and strategic clinical trial feasibility within the last 4 years. He provides extensive experience in integrating critical strategic and data elements into clinical trial strategies, including but not limited to disease background, competitive trial landscapes, epidemiology, standard of care, country experience, enrollment rate assessments, and recruitment projections. Dr. Pace has strategic feasibility experience across a variety of therapeutic areas, including neurology, psychiatry, rare disease, oncology/hematological malignancies, cardiovascular, renal/metabolic, and medical device. He earned his Bachelor of Science in Biology and Neuroscience from Indiana University and his Ph.D. in Biomedical Sciences from the University of Florida.