Optimizing Enrollment and Decision-Making in a Complex Glioblastoma Dose-Escalation Trial 

By Titia Tjeenk Willink, MSc, Senior Project Director, Global Project Leadership at Allucent

Study Background: 

Allucent was selected to perform a Phase I/II study in participants with glioblastoma for an emerging European biotech. Collaboration started early 2018 and FPI was enrolled later that year. 

• Design: Randomized, open-label, dose-escalation, dose-expansion study in patients with glioblastoma 
• Countries: Germany, Netherlands, France  
• Services: Full-Service 

Challenges Faced: Managing Cohort Logistics and Operational Barriers in a Complex Dose-Escalation Design 

One of the primary challenges in this study was ensuring continuous enrollment throughout the dose-escalation phase, as timelines are driven primarily by cohort logistics. Oncology clinical trials, particularly those involving dose escalation, often face significant hurdles in maintaining continuous enrollment. The complexity arises from the need to carefully manage cohort logistics, as each dose level must be evaluated for safety before progressing to the next dose level. This process can lead to delays, as patient enrollment is contingent on the completion of safety reviews and the availability of slots in each cohort. Additionally, the rarity of glioblastoma and the strict inclusion/exclusion criteria for this trial further narrowed the pool of eligible participants, making it challenging to maintain a steady flow of patients. These factors collectively created a bottleneck in enrollment, risking prolonged timelines and increased operational costs. 

Safety Review Committees (SRCs) play a critical role in oncology trials, ensuring patient safety and guiding dose-escalation decisions. However, coordinating SRC meetings can be a logistical challenge, particularly in multinational studies. Differences in time zones and the availability of key stakeholders often result in scheduling conflicts and delays. In dose-escalation studies, where timely decisions are crucial to advancing the trial, any delay in SRC meetings can have a cascading effect on the overall study timeline. In addition to scheduling challenges, electronic case report forms (eCRFs) must be completed in advance of SRCs to enable rapid data analysis for decision-making about the next dose level. Delays in data entry, inconsistencies in documentation, or a backlog in data review can impede the ability to make informed decisions about dose progression. 

Also crucial to the operational success of this glioblastoma study were strong logistics for collection of biological samples (PK samples), essential for quality endpoint data. Logistical challenges, such as ensuring proper sample handling, maintaining cold chain requirements, and coordinating shipments across multiple sites, can jeopardize sample integrity. In early phase oncology studies, where endpoint data is heavily reliant on these samples, any disruption in the logistics chain can compromise the quality of the data and the study’s outcomes. 

Solutions in Action: A Proactive, Integrated Approach to Sustaining Trial Momentum

Through a highly coordinated and proactive operational strategy, the study team successfully minimized typical delays associated with dose-escalation oncology clinical trials and maintained strong study momentum. 

A structured cohort management approach enabled continuous patient flow despite a relatively low recruitment rate.  An essential strategy to successful cohort management for this study was establishing clear and fair cohort enrollment rules which were communicated to the sites at the study start. We provided ‘slots’ to patients for a cohort based on a first-come basis. Patients not provided a slot, but potentially eligible, were kept on a pre-identification list or waiting list (at Investigator discretion). 

Equally important was proactivity in SRC planning. By scheduling meetings immediately upon enrollment of the last patient in the cohort and maintaining ongoing data readiness, the team reduced lag dose-escalation decisions. They minimized downtime by setting the meeting date as soon as the last patient in a cohort was enrolled.  

Additionally, rapid and accurate data availability was critical for the SRC, and the completion of time-sensitive eCRFs was paramount. Cross-functional collaboration among clinical, medical, data management, and biostatistics teams ensured that all data was reviewed on an ongoing basis to readily identify training needs, data entry backlogs, or other challenges that required attention. Quality data documentation sped up the ability to quickly evaluate a dose level.  In parallel, strengthened oversight of PK sample logistics ensured high-quality, reliable endpoint data. Well-organized support along with proper collection, processing, and shipment of samples ensured smooth processing and timely analysis. Allucent CRAs provided ongoing support to the site staff to ensure samples were collected per protocol requirements.   

Finally, through centralized communication and coordination, the team ensured that sites were kept apprised of the cohort status through weekly communication emails which provided updates on enrollment and slot assignments.  They also ensured that enrollment slot allocations flowed through a single point of contact to avoid any confusion. In addition to transparent communication with the sites, seamless internal communication between all involved departments, from medical to data management to CRAs, was essential for efficient enrollment, dosing and decision making.  

As a result, while dose-limiting toxicities (DLTs) inherently impacted progression timelines, the team effectively mitigated avoidable delays through anticipation, real-time oversight, and precise orchestration. Allucent’s proactive approach not only optimized cohort throughput but also ensured high-quality data delivery, demonstrating operational excellence in a complex early-phase oncology study.