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

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. GalskyRichard 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

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	271-286
Number of pages	16
Journal	Bladder Cancer
Volume	9
Issue number	3
DOIs	https://doi.org/10.3233/BLC-230056
State	Published - Sep 25 2023
Externally published	Yes

Keywords

anti-neoplastic agents
BCG
BCG-unresponsive
clinical trial design
regulatory

ASJC Scopus subject areas

Oncology
Urology

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10.3233/BLC-230056

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Chang, E., Hahn, N. M., Lerner, S. P., Fallah, J., Agrawal, S., Kamat, A. M., Bhatnagar, V., Svatek, R. S., Jaigirdar, A. A., Bross, P., Shore, N., Kates, M., Sachse, K., Brewer, J. R., O'donnell, M. A., Steinberg, G. D., Viviano, C. J., Bloomquist, E., Ribal, M. J., ... Weinstock, C. (2023). Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer. Bladder Cancer, 9(3), 271-286. https://doi.org/10.3233/BLC-230056

Chang, E, Hahn, NM, Lerner, SP, Fallah, J, Agrawal, S, Kamat, AM, Bhatnagar, V, Svatek, RS, Jaigirdar, AA, Bross, P, Shore, N, Kates, M, Sachse, K, Brewer, JR, O'donnell, MA, Steinberg, GD, Viviano, CJ, Bloomquist, E, Ribal, MJ, Galsky, MD, Oliver, R, Black, PC, Al-Ahmadie, H, Brothers, K, Pohar, K, Dinney, CP, Feng, Z, Downs, TM, Porten, SP, Smith, AB, Bangs, R, Psutka, SP, Agarwal, N, Amiri-Kordestani, L, Suzman, DL, Pazdur, R, Kluetz, PG & Weinstock, C 2023, 'Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer', Bladder Cancer, vol. 9, no. 3, pp. 271-286. https://doi.org/10.3233/BLC-230056

@article{ffa95652e0a74e44ae32742eec5a664f,

title = "Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer",

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-na{\"i}ve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-na{\"i}ve 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 = "anti-neoplastic agents, BCG, BCG-unresponsive, clinical trial design, regulatory",

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

note = "Publisher Copyright: {\textcopyright} 2023 - The authors. Published by IOS Press.",

year = "2023",

month = sep,

day = "25",

doi = "10.3233/BLC-230056",

language = "English (US)",

volume = "9",

pages = "271--286",

journal = "Bladder Cancer",

issn = "2352-3727",

publisher = "IOS Press",

number = "3",

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TY - JOUR

T1 - Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer

AU - Chang, Elaine

AU - Hahn, Noah M.

AU - Lerner, Seth P.

AU - Fallah, Jaleh

AU - Agrawal, Sundeep

AU - Kamat, Ashish M.

AU - Bhatnagar, Vishal

AU - Svatek, Robert S.

AU - Jaigirdar, Adnan A.

AU - Bross, Peter

AU - Shore, Neal

AU - Kates, Max

AU - Sachse, Karen

AU - Brewer, Jamie R.

AU - O'donnell, Michael A.

AU - Steinberg, Gary D.

AU - Viviano, Charles J.

AU - Bloomquist, Erik

AU - Ribal, Maria J.

AU - Galsky, Matthew D.

AU - Oliver, Richard

AU - Black, Peter C.

AU - Al-Ahmadie, Hikmat

AU - Brothers, Kenneth

AU - Pohar, Kamal

AU - Dinney, Colin P.

AU - Feng, Zhou

AU - Downs, Tracy M.

AU - Porten, Sima P.

AU - Smith, Angela B.

AU - Bangs, Rick

AU - Psutka, Sarah P.

AU - Agarwal, Neeraj

AU - Amiri-Kordestani, Laleh

AU - Suzman, Daniel L.

AU - Pazdur, Richard

AU - Kluetz, Paul G.

AU - Weinstock, Chana

PY - 2023/9/25

Y1 - 2023/9/25

N2 - 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.

AB - 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.

KW - anti-neoplastic agents

KW - BCG

KW - BCG-unresponsive

KW - clinical trial design

KW - regulatory

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DO - 10.3233/BLC-230056

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JO - Bladder Cancer

JF - Bladder Cancer

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ER -

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer

Abstract

Keywords

ASJC Scopus subject areas

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