A Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer

NCT03392428 | Completed Phase 2 DMC

• 1 other identifier: ANZUP 1603
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 11

Brief Summary

This open label, randomised, stratified, 2-arm, multicentre, phase 2 trial aims to determine the activity and safety of Lu-PSMA vs cabazitaxel in men with progressive metastatic castration resistant prostate cancer

Conditions

Cancer of the Prostate; Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Prostate Specific Antigen response rate (PSA RR)

  PSA RR defined as the proportion of participants in each group with a PSA reduction of ≥ 50% from baseline.

  Through study completion, on average 4 years

Secondary Outcomes (9)

• Pain Response (PPI and Analgesic Score)

  Through study completion, on average 4 years

• Objective Tumour Response Rate

  Through study completion, on average 4 years

• Progression free survival

  Through study completion, on average 4 years

• PSA progression free survival

  Through study completion, on average 4 years

• Pain progression free survival

  Through study completion, on average 4 years

Other Outcomes (2)

• Tertiary Correlative objectives: Associations between Ga-68 PSMA PET/CT, FDG-PET/CT baseline characteristics, and outcomes

  Through study completion, on average 4 years

• Tertiary Correlative objectives: Associations between clinical outcomes and possible prognostic and/or predictive biomarkers (tissue and circulating) including ctDNA

  Through study completion, on average 4 years

Study Arms (2)

177Lu-PSMA617

EXPERIMENTAL

Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles. The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.

Other: 177Lu-PSMA617

Cabazitaxel

ACTIVE COMPARATOR

Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles. Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.

Drug: Cabazitaxel

Interventions

177Lu-PSMA617 OTHER

Patients randomised to the 177Lu-PSMA617 arm will receive 6-8.5GBq of 177Lu-PSMA617 by intravenous injection once every 6 weeks until progressive disease, prohibitive toxicity or a maximum of 6 cycles. The first dose will be administered at 8.5GBq, reducing by 0.5GBq with every cycle given (i.e. to 6.0GBq on the sixth cycle, if reached). In some patients who have an exceptional response, treatment will be paused but can be re-commenced up to the maximum of 6 cycles upon progression.

Also known as: Lutetium Prostate-specific membrane antigen

177Lu-PSMA617

Cabazitaxel DRUG

Patients randomised to the Cabazitaxel arm will receive 20mg/m2 Cabazitaxel by intravenous infusion once every 3 weeks until progressive disease, prohibitive toxicity or a maximum of 10 cycles. Patients in this arm will also receive prednisolone 10mg orally per day for the duration of their cabazitaxel treatment.

Also known as: Jevtana

Cabazitaxel

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study is looking at prostate cancer which only affects males. The prostate gland is a male reproductive organ
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by:
• Documented histopathology of prostate adenocarcinoma OR
• Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes)
• Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) analog
• Progressive disease with rising PSA on 3 consecutive measurements, and PSA ≥ 20 ng/mL
• Target or non-target lesions according to RECIST 1.1
• Prior treatment with docetaxel
• Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax 20 at a site of disease, and SUVmax \> 10 at sites of measurable disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
• ECOG Performance status 0 to 2
• Assessed by a medical oncologist as suitable for chemotherapy with cabazitaxel
• Adequate renal function:
• Cr Cl ≥ 40mL/min (Cockcroft-Gault formula)
• Adequate bone marrow function:
• Platelets ≥ 100 x10 billion /L
• Hb ≥ 90g/L (no red blood cell transfusion in last 4 weeks)

You may not qualify if:

• Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
• Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity \> 68Ga-PSMA activity OR 68Ga-PSMA SUVmax \< 10
• Sjogren's syndrome
• Prior treatment with cabazitaxel or Lu-PSMA
• Contraindications to the use of corticosteroid treatment
• Active malignancy other than prostate cancer
• Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
• Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception

Sponsors & Collaborators

• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: lead
• Australian Nuclear Science and Technology Organisation (ANSTO): collaborator
• Endocyte: collaborator
• Prostate Cancer Foundation of Australia (PCFA): collaborator
• Australasian Radiopharmaceutical Trials network (ARTnet): collaborator
• Movember Foundation: collaborator

Study Sites (11)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle Hospital

Waratah, New South Wales, 2298, Australia

Location

Royal Brisbane and Womens Hospital

Brisbane, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3008, Australia

Location

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

Monash Moorabbin Hospital

Moorabbin, Victoria, 3165, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6450, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (7)

• Kwan EM, Ng SWS, Tolmeijer SH, Emmett L, Sandhu S, Buteau JP, Iravani A, Joshua AM, Francis RJ, Subhash V, Lee ST, Scott AM, Martin AJ, Stockler MR, Donnellan G, Annala M, Herberts C, Davis ID, Hofman MS, Azad AA, Wyatt AW; TheraP Investigators and the ANZUP Cancer Trials Group. Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial. Nat Med. 2025 Aug;31(8):2722-2736. doi: 10.1038/s41591-025-03704-9. Epub 2025 May 27.

  PMID: 40425844 DERIVED

• Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. doi: 10.1016/S1470-2045(23)00529-6. Epub 2023 Nov 30.

  PMID: 38043558 DERIVED

• Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon HM, Davis ID, Ralph N. Experiences of participants in a clinical trial of a novel radioactive treatment for advanced prostate cancer: A nested, qualitative longitudinal study. PLoS One. 2022 Nov 9;17(11):e0276063. doi: 10.1371/journal.pone.0276063. eCollection 2022.

  PMID: 36350899 DERIVED

• Buteau JP, Martin AJ, Emmett L, Iravani A, Sandhu S, Joshua AM, Francis RJ, Zhang AY, Scott AM, Lee ST, Azad AA, McJannett MM, Stockler MR, Williams SG, Davis ID, Hofman MS; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. Lancet Oncol. 2022 Nov;23(11):1389-1397. doi: 10.1016/S1470-2045(22)00605-2. Epub 2022 Oct 16.

  PMID: 36261050 DERIVED

• Viljoen B, Hofman MS, Chambers SK, Dunn J, Dhillon H, Davis ID, Ralph N. Advanced prostate cancer experimental radioactive treatment-clinical trial decision making: patient experiences. BMJ Support Palliat Care. 2021 Aug 9:bmjspcare-2021-002994. doi: 10.1136/bmjspcare-2021-002994. Online ahead of print.

  PMID: 34373282 DERIVED

• Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3. Epub 2021 Feb 11.

  PMID: 33581798 DERIVED

• Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.

  PMID: 31595044 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Pluvicto; cabazitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Hofman, A/Prof

  Peter MacCallum Cancer Centre, Melbourne, Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, randomised, stratified, 2-arm, phase 2 trial

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: January 8, 2018
• Study Start: January 29, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2021
• Last Updated: June 13, 2022

Record last verified: 2022-06

Locations

AU (11)