139th National Cancer Advisory Board
and products for clinical trials. The goal has been to use between $10 and $15 million per year of existing contract research resources.
There are eligibility requirements for participation in RAID. The program was designed such that only academic or nonprofit investigators may apply; it is expected that most applicants for activities funded by RAID will have an appointment in an institution with an NIH-assured IRB, or have formal collaborations with a staff member of such an institution. Research collaborations between academic and any size corporate partner are acceptable, provided that the technology is not yet licensed. Additionally, technology can be licensed to a small business (SBIR).
Dr. Tomaszewski next shared two examples of projects and their outcomes.
(1) Dr. Elizabeth Jaffe, Johns Hopkins, worked on an allogeneic pancreatic cancer vaccine. The background indicated that tumor cells that were genetically modified to secrete GM-CSF would generate a much more potent T cell response. It was not feasible, however, to accomplish this in an autologous fashion, as the cost and the amount of time involved, especially with pancreatic adenocarcinoma, was prohibitive. An allogeneic vaccine strategy, therefore, was adopted, and Dr. Jaffe requested production of two clinical grade GM-CSF secreting lines, which were designated as PANC 6.03 and 10.05, for treatment of pancreatic adenocarcinoma patients. Production conditions were established at the NCI FCRDC facilities by the Biopharmaceutical Development Program (BDP) to produce sterile lines suitable for human use. Approximately 240 vials of each cell line were produced. It took six production runs to produce one of the agents; the other one, which was a much more difficult process, took 12 runs to produce the materials. Additionally, a Drug Development Group (DDG) project was employed to produce sufficient material to conduct a Phase II trial in 60 patients. The preliminary analysis of these studies reveals that the 1- and 2-year survival rates are 88 and 76 percent, respectively.
(2) The work of Dr. Michael Sporn, Dartmouth, required the synthesis of some triterpenoids labeled as CDDO and CDDO methyl ester to allow in vivo preclinical testing. These particular triterpenoids bind to PPAR gamma, induce differentiation in several tumor types, and suppress the de novo synthesis of COX- 2 and iNOS. The application was submitted in February 1999 and reviewed in April; in October, 25 grams of each compound were delivered to Dr. Sporn. He completed in vivo studies with both agents and returned to the NCI in April 2001 for further preclinical and clinical development through the DDG. NCI’s IND was filed and approved earlier this year, and there are two Phase I trials open. To date 10 patients have been treated with this particular agent.
RAID has funded 16 cycles, in which 336 applications have been received and 119 of those have been approved. To date, 81 projects have been completed and 35 INDs have been filed and approved by the FDA. More than 1,600 patients have been treated with these agents and, through interactions with the program, 28 of these agents have been licensed. The cost for the entire program has been about $91 million.
Report of the Workshop To Review the NCI’s RAID Program. Dr. Mendelsohn served as Chair of the workshop. He noted that Drs. Bill Hait and Lou Weiner chaired subcommittees on small molecules and biologics, respectively. There also was tremendous interest and participation by NCI staff representatives, as well as staff support. At the workshop, held on July 13, 2005, participants were asked to review the goals, operations, and track record of RAID, and to make recommendations.
Several major issues were identified during the workshop and are summarized in the workshop report. (1) The endpoint should be entry into Phase 0/I clinical trials. (2) Review and oversight should involve continuity rather than ad hoc evaluation; yearly checks on progress; and tougher enforcement to