TheraP: a randomized phase 2 trial of 177Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

Michael S. Hofman, Louise Emmett, John Violet, Alison Y. Zhang, Nicola J. Lawrence, Martin Stockler, Roslyn J. Francis, Amir Iravani, Scott Williams, Arun Azad, Andrew Martin, Margaret McJannett, ANZUP TheraP team, Ian D. Davis

Research output: Contribution to journalArticleOtherpeer-review

2 Citations (Scopus)

Abstract

Objective: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Patients and methods: The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68Ga-PSMA-11 and Fluorine-18 (18F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. Results and Conclusions: 177Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

Original languageEnglish
Pages (from-to)5-13
Number of pages9
JournalBJU International
Volume124
Issue numberS1
DOIs
Publication statusPublished - Nov 2019
EventGenitourinary Cancers Symposium 2019 - San Francisco, United States of America
Duration: 14 Feb 201916 Feb 2019

Keywords

  • #ProstateCancer
  • cabazitaxel
  • castration-resistant
  • prostate cancer
  • PSMA
  • theranostics

Cite this

Hofman, Michael S. ; Emmett, Louise ; Violet, John ; Y. Zhang, Alison ; Lawrence, Nicola J. ; Stockler, Martin ; Francis, Roslyn J. ; Iravani, Amir ; Williams, Scott ; Azad, Arun ; Martin, Andrew ; McJannett, Margaret ; ANZUP TheraP team ; Davis, Ian D. / TheraP : a randomized phase 2 trial of 177Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603). In: BJU International. 2019 ; Vol. 124, No. S1. pp. 5-13.
@article{3f3b8f0b84be40a391fa75b8a9fa335d,
title = "TheraP: a randomized phase 2 trial of 177Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)",
abstract = "Objective: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Patients and methods: The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68Ga-PSMA-11 and Fluorine-18 (18F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. Results and Conclusions: 177Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.",
keywords = "#ProstateCancer, cabazitaxel, castration-resistant, prostate cancer, PSMA, theranostics",
author = "Hofman, {Michael S.} and Louise Emmett and John Violet and {Y. Zhang}, Alison and Lawrence, {Nicola J.} and Martin Stockler and Francis, {Roslyn J.} and Amir Iravani and Scott Williams and Arun Azad and Andrew Martin and Margaret McJannett and {ANZUP TheraP team} and Davis, {Ian D.}",
year = "2019",
month = "11",
doi = "10.1111/bju.14876",
language = "English",
volume = "124",
pages = "5--13",
journal = "BJU International",
issn = "1464-4096",
publisher = "Wiley-Blackwell",
number = "S1",

}

Hofman, MS, Emmett, L, Violet, J, Y. Zhang, A, Lawrence, NJ, Stockler, M, Francis, RJ, Iravani, A, Williams, S, Azad, A, Martin, A, McJannett, M, ANZUP TheraP team & Davis, ID 2019, 'TheraP: a randomized phase 2 trial of 177Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)', BJU International, vol. 124, no. S1, pp. 5-13. https://doi.org/10.1111/bju.14876

TheraP : a randomized phase 2 trial of 177Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603). / Hofman, Michael S.; Emmett, Louise; Violet, John; Y. Zhang, Alison; Lawrence, Nicola J.; Stockler, Martin; Francis, Roslyn J.; Iravani, Amir; Williams, Scott; Azad, Arun; Martin, Andrew; McJannett, Margaret; ANZUP TheraP team ; Davis, Ian D.

In: BJU International, Vol. 124, No. S1, 11.2019, p. 5-13.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - TheraP

T2 - a randomized phase 2 trial of 177Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

AU - Hofman, Michael S.

AU - Emmett, Louise

AU - Violet, John

AU - Y. Zhang, Alison

AU - Lawrence, Nicola J.

AU - Stockler, Martin

AU - Francis, Roslyn J.

AU - Iravani, Amir

AU - Williams, Scott

AU - Azad, Arun

AU - Martin, Andrew

AU - McJannett, Margaret

AU - ANZUP TheraP team

AU - Davis, Ian D.

PY - 2019/11

Y1 - 2019/11

N2 - Objective: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Patients and methods: The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68Ga-PSMA-11 and Fluorine-18 (18F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. Results and Conclusions: 177Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

AB - Objective: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Patients and methods: The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68Ga-PSMA-11 and Fluorine-18 (18F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. Results and Conclusions: 177Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

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KW - cabazitaxel

KW - castration-resistant

KW - prostate cancer

KW - PSMA

KW - theranostics

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DO - 10.1111/bju.14876

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