Case Study: Delivering two prostate cancer trials at scale

Developing a precision oncology radiopharmaceutical (RPT) is operationally complex, so sponsors must manage risks at every phase of clinical development and execution. Over the past five years, Parexel has completed more than 20 RPT oncology projects for sponsors, involving more than 2,100 patients at over 600 sites in 20 countries. Recently, we helped a biotech company conduct two large, late-stage trials of an RPT imaging agent for prostate cancer. Here is how we did it:

Context: Pivotal Prostate Cancer Trials

• An emerging biopharmaceutical company engaged Parexel to conduct two pivotal Phase III trials of a targeted radioisotope-labeled imaging agent to detect, stage, and localize initial and recurrent prostate cancer.
• The trials were each designed to enroll more than 350 patients. To facilitate the sponsor’s regulatory submission strategy, they were to run simultaneously over two years, ending in the same month.
• The trials enrolled patients at sites in Germany, Finland, the Netherlands, and the United States.

Challenges: Unique Trial Complexities

• Short IP shelf life. The investigational product (IP) had an eight-hour shelf life (later extended to 12 hours). It had to be administered, and protocol-specified positron emission tomography (PET) scans had to be performed on the day it was shipped. This resulted in complex manufacturing and site visit scheduling; for example, sites had to reserve PET scan slots in alignment with the shipping schedule.
• Multiple medical specialties. The trial's primary investigators (PIs) included radiologists, nuclear medicine physicians, and urologists, disciplines that are not always accustomed to or adept at working together.
• High volume of imaging data. The images from baseline and protocol-specified PET scans had to be read by three blinded external readers under tight deadlines in a process managed by a vendor.
• Differing requirements by country. National radioactive material (RAM) licensing requirements, site-level RAM review committee requirements, and protocol-specific requirements differed among the countries where trial sites were located.

Solutions and Results: Precision Planning Pays Off

Strategic foresight and meticulous execution were key to overcoming the unique challenges of these prostate cancer trials. The following sections detail how targeted solutions in logistics, cross-specialty collaboration, imaging data management, and regulatory navigation directly contributed to the trials' success.

1. Overcoming the Short Shelf Life: A Logistics Masterclass. The investigational product had a lifespan of eight hours (later extended to twelve), posing a significant logistical challenge. We addressed this with a site selection strategy that focused on a mix of academic and non-academic centers near manufacturing hubs in each country. We organized patient treatment days to coincide with IP production on Tuesdays and Thursdays, which allowed site visits to be scheduled effectively. We established strong communication channels between IP production vendors and site study teams at the start. Site staff updated patients about the limited scheduling flexibility due to manufacturing constraints and confirmed details multiple times. We performed dry runs of RAM delivery to anticipate and troubleshoot problems.
   The result? An impressive record of timely IP shipment and administration for both studies, with minimal disruptions and trial integrity upheld.
2. Bridging Medical Specialties: Leveraging Collaborative Expertise. Prostate cancer trials require collaboration between urologists and oncologists (who identify patients), and nuclear medicine specialists and radiologists (who perform PET scans). Since these specialties don't always align, our experienced medical monitor engaged urologist PIs from group practices in the U.S., which are key referral sources. Our PI selection guidelines targeted sites with a history of effective urology-radiology collaboration.
   The result? Urology-affiliated sites emerged as top recruiters, averaging 14 patients per site, significantly higher than others. Additionally, the strong rapport between urologists and patients helped recruit and retain participants. This collaboration also streamlined data entry, enabling one trial to achieve its last patient first visit (LPFV) milestone 45 days early. Overall enrollment in both trials significantly exceeded industry benchmarks.
3. Mastering Imaging Data Management: Transparency and Partnership. The volume of imaging data from PET scans required review by three independent, blinded readers under strict deadlines. To mitigate delays, we provided imaging vendors with comprehensive guidelines for clarity and timelines and set expectations for frequent, transparent updates. We fostered strong relationships with them, emphasizing open communication and proactive problem-solving for data quality and analysis readiness.
   The result? Imaging data for both trials were processed within the tight timelines. Trusted, collaborative partnerships were pivotal to smooth operations.
4. Navigating the Regulatory Maze: Expertise in Radioactive Material Handling. National radioactive material (RAM) regulations required close attention. Our team of former regulators and experts provided invaluable guidance in site selection, particularly with navigating Germany's Bundesamt für Strahlenschutz (BfS) requirements. We tailored our approach to accommodate the need for extensive documentation and approvals for RAM activities. German sites used on-site IP production pharmacies, while others with different regulations relied on off-site vendors. We adjusted trial start dates to accommodate the timelines for RAM licenses and isotope certifications.
   The result? Both trials met site initiation and patient enrollment targets in all four countries, and there were no delays from RAM licensing issues.

Meticulous planning, strategic site selection with a focus on collaborative specialties, proactive vendor management, and deep regulatory expertise weren't just boxes ticked – they were the levers that enabled these critical prostate cancer trials to execute successfully.

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