Clinical Trial Design for the Development of New Therapies for Nonmuscle-invasive Bladder Cancer: Report of a Food and Drug Administration and American Urological Association Public Workshop
Jarow JP1, Lerner SP2, Kluetz PG3, Liu K4, Sridhara R5, Bajorin D6, Chang S7, Dinney CP8, Groshen S9, Morton RA10, O'Donnell M11, Quale DZ12, Schoenberg M13, Seigne J14, Vikram B15. Urology. 2013 Dec 11. pii: S0090-4295(13)01375-7. doi: 10.1016/j.urology.2013.10.030. [Epub ahead of print]

Author information

1Office of Hematology and Oncology Products, Food and Drug Administration, Silver Spring, MD. Electronic address: 2Scott Department of Urology, Baylor College of Medicine Medical Center, Houston, TX. 3Office of Hematology and Oncology Products, Food and Drug Administration, Silver Spring, MD. 4Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD. 5Division of Biometrics V, Office of Biostatistics, CDER, Food and Drug Administration, Silver Spring, MD. 6Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY. 7Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN. 8The University of Texas MD Anderson Cancer Center, Houston, TX. 9Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, USC/Keck School of Medicine, Los Angeles, CA. 10American Medical Systems, Minnetonka, MN. 11University of Iowa, Iowa city, IA. 12Bladder Cancer Advocacy Network, Bethesda, MD. 13The Johns Hopkins University School of Medicine, Baltimore, MD. 14Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH. 15National Cancer Institute, Bethesda, MD.


OBJECTIVE: To summarize the discussion at a public workshop, cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association, reviewing potential trial designs for the development of new therapies for non-muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for NMIBC in the last 30 years, and product development for this disease has been stymied by difficulties in trial design and patient accrual.

METHODS: A workshop evaluating potential trial design for the development of therapies for NMIBC was held in San Diego, CA, in May 2013. Invited experts representing all stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates, discussed development of products for all risk strata of NMIBC.

RESULTS: The panel responded to specific questions from the FDA, discussing eligibility criteria, efficacy endpoints, and trial design for patients with a mix of high-grade papillary disease and carcinoma in situ, Bacillus Calmette-Guerin (BCG)-refractory disease, and intermediate-risk disease. Panel members also addressed the magnitude of response that would be clinically meaningful for various disease strata and trial design options for perioperative intravesical chemotherapy instillation at the time of resection of bladder tumors.

CONCLUSION: Expert commentary provided by panel members will inform a planned FDA guidance on pathways for drug and biologic development for NMIBC and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products for this disease.