Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer

Elaine Chang; Noah M Hahn; Seth P Lerner; Jaleh Fallah; Sundeep Agrawal; Ashish M Kamat; Vishal Bhatnagar; Robert S Svatek; Adnan A Jaigirdar; Peter Bross; Neal Shore; Max Kates; Karen Sachse; Jamie R Brewer; Michael A O'Donnell; Gary D Steinberg; Charles J Viviano; Erik Bloomquist; Maria J Ribal; Matthew D Galsky; Richard Oliver; Peter C Black; Hikmat Al-Ahmadie; Kenneth Brothers; Kamal Pohar; Colin P Dinney; Zhou Feng; Tracy M Downs; Sima P Porten; Angela B Smith; Rick Bangs; Sarah P Psutka; Neeraj Agarwal; Laleh Amiri-Kordestani; Daniel L Suzman; Richard Pazdur; Paul G Kluetz; Chana Weinstock

doi:10.3233/BLC-230056

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer

Bladder Cancer. 2023 Sep 25;9(3):271-286. doi: 10.3233/BLC-230056. eCollection 2023.

Authors

Elaine Chang¹, Noah M Hahn², Seth P Lerner³, Jaleh Fallah¹, Sundeep Agrawal¹, Ashish M Kamat⁴, Vishal Bhatnagar⁵, Robert S Svatek⁶, Adnan A Jaigirdar⁷, Peter Bross⁷, Neal Shore⁸, Max Kates⁹, Karen Sachse¹⁰, Jamie R Brewer¹, Michael A O'Donnell¹¹, Gary D Steinberg¹², Charles J Viviano¹³, Erik Bloomquist¹, Maria J Ribal¹⁴, Matthew D Galsky¹⁵, Richard Oliver^{1

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24}, Peter C Black¹⁶, Hikmat Al-Ahmadie¹⁷, Kenneth Brothers¹⁸, Kamal Pohar¹⁹, Colin P Dinney⁴, Zhou Feng¹, Tracy M Downs²⁰, Sima P Porten²¹, Angela B Smith²², Rick Bangs¹⁰, Sarah P Psutka²³, Neeraj Agarwal²⁴, Laleh Amiri-Kordestani¹, Daniel L Suzman¹, Richard Pazdur⁵, Paul G Kluetz⁵, Chana Weinstock¹

Affiliations

¹ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
² Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
³ Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
⁴ Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Oncology Center of Excellence, Food and Drug Administration, Silver Spring, MD, USA.
⁶ Department of Urology, University of Texas Health San Antonio, San Antonio, TX, USA.
⁷ Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁸ Department of Urology, Carolina Urologic Research Center, Myrtle Beach, SC, USA.
⁹ Department of Urology, Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Bladder Cancer Advocacy Network, Bethesda, MD, USA.
¹¹ Department of Urology, University of Iowa, Iowa City, IA, USA.
¹² Goldstein Bladder Cancer Program, NYU Langone Health, NYU Urology Associates, New York, NY, USA.
¹³ Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA.
¹⁴ Uro-Oncology Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.
¹⁵ Hematology-Oncology, Icahn School of Medicine at Mount Sinai/Tisch Cancer Institute, New York, NY, USA.
¹⁶ Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
¹⁷ Department of Pathology and Laboratory Medicine, Genitourinary Pathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁸ National Cancer Institute Bladder Cancer Task Force, Bethesda, MD, USA.
¹⁹ Department of Urology, The Ohio State University, Columbus, OH, USA.
²⁰ Department of Urology, University of Virginia, Charlottesville, VA, USA.
²¹ Department of Urology, University of California San Francisco, San Francisco, CA, USA.
²² Department of Urology, University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
²³ Department of Urology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA.
²⁴ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Abstract

Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.

Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.

Methods: Representatives from various disciplines including urologists, oncologists, pathologists, statisticians, basic and translational scientists, and the patient advocacy community participated. The workshop format included invited lectures, panel discussions, and opportunity for audience discussion and comment.

Results: In a pre-workshop survey, 92% of urologists surveyed considered the development of alternatives to BCG as a high drug development priority for BCG-naïve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-naïve NMIBC, BCG-unresponsive carcinoma in situ, and BCG-unresponsive papillary carcinoma; strengths and limitations of single-arm trial designs; assessing patient-reported outcomes; and considerations for assessing avoidance of cystectomy as an efficacy measure.

Conclusions: The workshop discussed several important opportunities for trial design refinement in NMIBC. FDA encourages sponsors to meet with the appropriate review division to discuss trial design proposals for NMIBC early in drug development.

Keywords: BCG; BCG-unresponsive; anti-neoplastic agents; clinical trial design; regulatory.