The PCCTC is the first clinical consortium created for the specific purpose of early drug development in a genitourinary malignancy. Over the past 3 years, the 10 participating sites have opened 51 studies through the Consortium—7 of which are first use in humans, and 22 of which are first use in prostate cancer. To date, 1386 patients have been enrolled. The focus of the PCCTC is specifically early-stage trials, which typically are complex and involve numerous scientific or correlative endpoints but are small in size. Such trials might require only a small number of collaborating centers to contribute patients, but these centers must closely coordinate to share registration information, adverse event reporting, and specimen tracking.
The PCCTC has developed the fundamental infrastructure needed to support early-phase, collaborative, interinstitutional studies. It has developed informatics systems to track clinical trial registration and accrual, capture electronic data in line with caBIG, CDISC, and FDA requirements, and track biospecimens. Further, it has defined CDEs, developed a shared protocol template, centralized protocol budgeting, formulated a legal framework to manage intellectual property, implemented a system of scientific review and prioritization, and developed administrative systems to allow for interinstitutional protocol development and scientific exchange.
For prostate cancer, the need for a consortium has been particularly pressing. Unlike clinical studies in other cancers, prostate cancer clinical trials have suffered from intrinsic difficulties in design that have delayed drug development. The disease has a uniquely diverse natural history, a distribution of disease that is singularly difficult to measure, and a highly variable underlying biology. The urgency to build a consortium has been amplified by the availability of an unprecedented number of drugs now available for testing. As a consortium, we have pooled resources for selecting the most promising drug candidates, designed and executed early-phase trials, and decided which drugs deserve to advance to larger phase III trials.
Lastly, clinical trial design for prostate cancer has evolved to the point of requiring formal coordination. Because the disease is bone-tropic and not amenable to standard response criteria, early readouts on clinical activity are difficult to identify.9–12
As a result, consensus criteria have been designed by leaders in the field,12–14
and these same leaders have collaborated through the PCCTC to update these criteria, implement unique study designs and develop and validate meaningful clinical endpoints.15
The PCCTC is, on a national level, standardizing clinical trial design, developing novel targets and measures of treatment effect, and prioritizing therapeutic approaches.
Although prostate cancer has several SPORE programs, the primary, though not exclusive, focus of these programs is scientific development rather than clinical trials. At the other end of the spectrum, the focus of the cooperative groups is on phase III trials rather than early drug development. The PCCTC fills, therefore, an important need, bridging the gap between basic science and large randomized clinical trials.
The idea of creating a disease-specific clinical consortium is not novel. Such consortia exist for relatively uncommon diseases, such as sarcoma (Sarcoma Alliance for Research through Collaboration), myeloma (Multiple Myeloma Research Consortium), and central nervous system (CNS) tumors (the New Approaches to Brain Tumor Therapy CNS Consortium and the Pediatric Brain Tumor Consortium), as well as common solid tumors such as lung cancer (International Lung Cancer Consortium) and breast cancer (Breast Cancer Surveillance Consortium).
The future direction of the PCCTC will, by necessity, be different from its past. The consortium was established by a granting mechanism from the DOD with additional funding from the Prostate Cancer Foundation. Future viability will rely on developing a financial plan in which the PCCTC is not reliant on a single set of funds. In the process, the PCCTC will have an opportunity to redefine its measures of success. As the PCCTC matures, its focus will shift toward enhancing a common clinical trial database, tissue collection and analysis, designing clinical trials around scientific themes, and building an auditing mechanism for data verification of investigator-sponsored studies. We will focus increasingly on accruing patients from underserved communities, and plan to expand patient access to our studies beyond the present 10 research centers.