A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984

Prashant Patel; JG Young; Vivien Mautner; D Ashdown; Sarah Bonney; RG Pineda; Stuart Collins; Peter Searle; Diana Hull; E Peers; J Chester; David Wallace; A Doherty; H Leung; Lawrence Young; Nicholas James

doi:10.1038/mt.2009.80

A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984

Prashant Patel, JG Young, Vivien Mautner^*, D Ashdown, Sarah Bonney, RG Pineda, Stuart Collins, Peter Searle, Diana Hull, E Peers, J Chester, David Wallace, A Doherty, H Leung, Lawrence Young, Nicholas James

^*Corresponding author for this work

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Abstract

We report a phase I/II clinical trial in prostate cancer (PCa) using direct intraprostatic injection of a replication defective adenovirus vector (CTL102) encoding bacterial nitroreductase (NTR) in conjunction with systemic prodrug CB1954. One group of patients with localized PCa scheduled for radical prostatectomy received virus alone, prior to surgery, in a dose escalation to establish safety, tolerability, and NTR expression. A second group with local failure following primary treatment received virus plus prodrug to establish safety and tolerability. Based on acceptable safety data and indications of prostate-specific antigen (PSA) responses, an extended cohort received virus at a single dose level plus prodrug. The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Immunohistochemistry of resected prostate demonstrated NTR staining in tumor and glandular epithelium at all dose levels [5 x 10(10)-1 x 10(12) virus particles (vp)]. A total of 19 patients received virus plus prodrug and 14 of these had a repeat treatment; minimal toxicity was observed and there was preliminary evidence of change in PSA kinetics, with an increase in the time to 10% PSA progression in 6 out of 18 patients at 6 months.Molecular Therapy (2009); doi:10.1038/mt.2009.80.

Original language	English
Pages (from-to)	1292-9
Number of pages	8
Journal	Molecular Therapy
Volume	17
Issue number	7
DOIs	https://doi.org/10.1038/mt.2009.80
Publication status	Published - 14 Apr 2009

Bibliographical note

Corrigendum:
Corrigendum to “A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase With CB1984”, Molecular Therapy,
Volume 17, Issue 7, 2009, Page 1302, ISSN 1525-0016,
https://doi.org/10.1038/mt.2009.110.
Pure record # 169944163

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Patel, P., Young, JG., Mautner, V., Ashdown, D., Bonney, S., Pineda, RG., Collins, S., Searle, P., Hull, D., Peers, E., Chester, J., Wallace, D., Doherty, A., Leung, H., Young, L., & James, N. (2009). A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984. Molecular Therapy, 17(7), 1292-9. https://doi.org/10.1038/mt.2009.80

@article{6128caf8f9e14a44af1accb4b1d01dc9,

title = "A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984",

abstract = "We report a phase I/II clinical trial in prostate cancer (PCa) using direct intraprostatic injection of a replication defective adenovirus vector (CTL102) encoding bacterial nitroreductase (NTR) in conjunction with systemic prodrug CB1954. One group of patients with localized PCa scheduled for radical prostatectomy received virus alone, prior to surgery, in a dose escalation to establish safety, tolerability, and NTR expression. A second group with local failure following primary treatment received virus plus prodrug to establish safety and tolerability. Based on acceptable safety data and indications of prostate-specific antigen (PSA) responses, an extended cohort received virus at a single dose level plus prodrug. The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Immunohistochemistry of resected prostate demonstrated NTR staining in tumor and glandular epithelium at all dose levels [5 x 10(10)-1 x 10(12) virus particles (vp)]. A total of 19 patients received virus plus prodrug and 14 of these had a repeat treatment; minimal toxicity was observed and there was preliminary evidence of change in PSA kinetics, with an increase in the time to 10% PSA progression in 6 out of 18 patients at 6 months.Molecular Therapy (2009); doi:10.1038/mt.2009.80.",

author = "Prashant Patel and JG Young and Vivien Mautner and D Ashdown and Sarah Bonney and RG Pineda and Stuart Collins and Peter Searle and Diana Hull and E Peers and J Chester and David Wallace and A Doherty and H Leung and Lawrence Young and Nicholas James",

note = "Corrigendum: Corrigendum to “A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase With CB1984”, Molecular Therapy, Volume 17, Issue 7, 2009, Page 1302, ISSN 1525-0016, https://doi.org/10.1038/mt.2009.110. Pure record # 169944163",

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day = "14",

doi = "10.1038/mt.2009.80",

language = "English",

volume = "17",

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Patel, P, Young, JG, Mautner, V, Ashdown, D, Bonney, S, Pineda, RG, Collins, S, Searle, P, Hull, D, Peers, E, Chester, J, Wallace, D, Doherty, A, Leung, H, Young, L & James, N 2009, 'A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984', Molecular Therapy, vol. 17, no. 7, pp. 1292-9. https://doi.org/10.1038/mt.2009.80

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AU - Young, JG

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AU - Ashdown, D

AU - Bonney, Sarah

AU - Pineda, RG

AU - Collins, Stuart

AU - Searle, Peter

AU - Hull, Diana

AU - Peers, E

AU - Chester, J

AU - Wallace, David

AU - Doherty, A

AU - Leung, H

AU - Young, Lawrence

AU - James, Nicholas

N1 - Corrigendum: Corrigendum to “A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase With CB1984”, Molecular Therapy, Volume 17, Issue 7, 2009, Page 1302, ISSN 1525-0016, https://doi.org/10.1038/mt.2009.110. Pure record # 169944163

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N2 - We report a phase I/II clinical trial in prostate cancer (PCa) using direct intraprostatic injection of a replication defective adenovirus vector (CTL102) encoding bacterial nitroreductase (NTR) in conjunction with systemic prodrug CB1954. One group of patients with localized PCa scheduled for radical prostatectomy received virus alone, prior to surgery, in a dose escalation to establish safety, tolerability, and NTR expression. A second group with local failure following primary treatment received virus plus prodrug to establish safety and tolerability. Based on acceptable safety data and indications of prostate-specific antigen (PSA) responses, an extended cohort received virus at a single dose level plus prodrug. The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Immunohistochemistry of resected prostate demonstrated NTR staining in tumor and glandular epithelium at all dose levels [5 x 10(10)-1 x 10(12) virus particles (vp)]. A total of 19 patients received virus plus prodrug and 14 of these had a repeat treatment; minimal toxicity was observed and there was preliminary evidence of change in PSA kinetics, with an increase in the time to 10% PSA progression in 6 out of 18 patients at 6 months.Molecular Therapy (2009); doi:10.1038/mt.2009.80.

AB - We report a phase I/II clinical trial in prostate cancer (PCa) using direct intraprostatic injection of a replication defective adenovirus vector (CTL102) encoding bacterial nitroreductase (NTR) in conjunction with systemic prodrug CB1954. One group of patients with localized PCa scheduled for radical prostatectomy received virus alone, prior to surgery, in a dose escalation to establish safety, tolerability, and NTR expression. A second group with local failure following primary treatment received virus plus prodrug to establish safety and tolerability. Based on acceptable safety data and indications of prostate-specific antigen (PSA) responses, an extended cohort received virus at a single dose level plus prodrug. The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Immunohistochemistry of resected prostate demonstrated NTR staining in tumor and glandular epithelium at all dose levels [5 x 10(10)-1 x 10(12) virus particles (vp)]. A total of 19 patients received virus plus prodrug and 14 of these had a repeat treatment; minimal toxicity was observed and there was preliminary evidence of change in PSA kinetics, with an increase in the time to 10% PSA progression in 6 out of 18 patients at 6 months.Molecular Therapy (2009); doi:10.1038/mt.2009.80.

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DO - 10.1038/mt.2009.80

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C2 - 19367257

SN - 1525-0024

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EP - 1299

JO - Molecular Therapy

JF - Molecular Therapy

IS - 7

ER -

A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984

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