Enzalutamide With Lu PSMA-617 Versus Enzalutamide Alone in Men With Metastatic Castration-resistant Prostate Cancer

NCT04419402 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ANZUP 1901
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 15

Brief Summary

This phase 2 randomised clinical trial will investigate the activity and safety of adding Lu-PSMA to enzalutamide in patients with metastatic castrate resistant prostate cancer (mCRPC) not previously treated with chemotherapy.

Conditions

Metastatic Castration-Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Prostate Specific Antigen (PSA) Progression-Free Survival

  PSA progression is defined as a rise in PSA by more than or equal to 25% AND more than or equal to 2 ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later.

  Date of randomisation to the date of first evidence of PSA progression - assessed up to study completion, approximately 4 years from recruitment.

Secondary Outcomes (6)

• Radiographic Progression-Free Survival

  Date of randomisation to the date of first evidence of radiographic progression on imaging. Assessed every 12 weeks through study completion, approximately 4 years from start of recruitment.

• Prostate Specific Antigen (PSA) response rate

  Date of randomisation through study completion, approximately 4 years from start of recruitment. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA response

• Pain response and Progression-Free Survival

  Date of randomisation through study completion, approximately 4 years from start of recruitment

• Clinical Progression-Free Survival

  Date of randomisation to the date of first clinical evidence of disease progression or death from any cause. Assessed up to study completion approximately 4 years from recruitment.

• Aspects of Health-related Quality of life (HRQL)

  Assessed every 4-6 weeks, through study completion, approximately 4 years from recruitment.

Other Outcomes (4)

• Overall Survival

  Through study completion, approximately 4 years from recruitment.

• Resource Use and Incremental Cost-effectiveness

  Through study completion, approximately 4 years from recruitment.

• Association between Clinical Outcomes and Imaging Analyses at Baseline and During Treatment

  Through study completion, approximately 4 years from recruitment.

Study Arms (2)

Lu-PSMA + Enzalutamide

EXPERIMENTAL

Lu-PSMA - 7.5 GBq (± 10%): doses 1 and 2 (Days 15 and 57). Doses 3 and 4 (Days 113 and 169) will be given following result of PSMA PET/CT scans at Day 92. Enzalumatide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.

Drug: Lu-PSMA; Drug: Enzalutamide

Enzalutamide

ACTIVE COMPARATOR

Enzalutamide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.

Drug: Enzalutamide

Interventions

Lu-PSMA DRUG

Patients will be given 7.5 GBq of Lu-PSMA in 4 doses. Dose 1 and 2 on Days 15 and 57. Doses 3 and 4 (Days 113 and 169) will be given following result of 68Ga-PSMA PET/CT at Day 92. Treatment administered every 6 weeks, x 4 cycles.

Also known as: 177Lutetium -PSMA 617 also referred to as 177Lu-PSMA

Lu-PSMA + Enzalutamide

Enzalutamide DRUG

160 mg (four 40 mg capsules) daily.

Also known as: Xtandi

Enzalutamide; Lu-PSMA + Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Men with mCRPC not previously treated with docetaxel for castration-resistant disease, suitable for treatment with enzalutamide and Lu-PSMA.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged 18 or older with metastatic adenocarcinoma of the prostate defined by:
• Documented histopathology of prostate adenocarcinoma (no features of neuroendocrine carcinoma) OR
• Metastatic disease typical of prostate cancer
• Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
• Progressive disease with rising PSA defined by PCWG3 criteria (sequence of 2 rising values at a minimum of 1-week intervals) AND PSA ≥ 5 ng/mL.
• At least 2 of the following risk factors for early treatment failure with enzalutamide:
• LDH ≥ ULN
• ALP ≥ ULN
• Albumin \<35 g/L
• De novo metastatic disease (M1) at initial diagnosis \*
• \<3 years since initial diagnosis
• \>5 bone metastases \*
• Visceral metastases \*
• PSA doubling time \<84 days
• Pain requiring opiates for \>14 days

You may not qualify if:

• Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate
• Ga-PSMA PET/CT SUVmax \< 10 at a site of measurable disease \> 10mm
• Prior treatment with enzalutamide, darolutamide, or apalutamide. Prior treatment with abiraterone is allowed.
• Prior treatment with any PSMA-targeted radiotherapy
• Prior chemotherapy for mCRPC. Prior docetaxel in castration-sensitive setting is permitted
• History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours)
• 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
• Men in sexual relationships with women of reproductive potential who are not willing/able to use medically acceptable forms of barrier contraception
• History of:
• seizure or any condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
• loss of consciousness or transient ischemic attack within 12 months of randomization
• significant cardiovascular disease within the last 3 months: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater, see Appendix 4), ongoing arrhythmias of Grade \> 2, thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed

Sponsors & Collaborators

• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: lead
• National Health and Medical Research Council, Clinical Trials Centre: collaborator
• Prostate Cancer Research Alliance: collaborator
• Endocyte: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (15)

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Northern Cancer Institute

Sydney, New South Wales, 2065, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

Location

Related Publications (3)

• Emmett L, Papa N, Subramaniam S, Crumbaker M, Nguyen A, Joshua AM, Sandhu S, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ayati N, Niu C, Hofman MS, Martin AJ, Thomas H, Davis ID, Stockler MR; ENZA-p Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Prognostic and predictive value of baseline PSMA-PET total tumour volume and SUVmean in metastatic castration-resistant prostate cancer in ENZA-p (ANZUP1901): a substudy from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2025 Sep;26(9):1168-1177. doi: 10.1016/S1470-2045(25)00339-0. Epub 2025 Jul 30.

  PMID: 40752515 DERIVED

• Emmett L, Subramaniam S, Crumbaker M, Joshua AM, Sandhu S, Nguyen A, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Gedye C, Rutherford NK, Kumar ASR, Pook D, Ramdave S, Nadebaum DP, Voskoboynik M, Redfern AD, Macdonald W, Krieger L, Schembri G, Chua W, Lin P, Horvath L, Bastick P, Butler P, Zhang AY, McJannett M, Thomas H, Langford A, Hofman MS, Martin AJ, Davis ID, Stockler MR; ENZA-p Trial Investigators; Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival and quality of life with [177Lu]Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer (ENZA-p): secondary outcomes from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2025 Mar;26(3):291-299. doi: 10.1016/S1470-2045(25)00009-9. Epub 2025 Feb 13.

  PMID: 39956124 DERIVED

• Emmett L, Subramaniam S, Crumbaker M, Nguyen A, Joshua AM, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Gedye C, Rutherford NK, Sandhu S, Kumar AR, Pook D, Ramdave S, Nadebaum DP, Voskoboynik M, Redfern AD, Macdonald W, Krieger L, Schembri G, Chua W, Lin P, Horvath L, Bastick P, Butler P, Zhang AY, Yip S, Thomas H, Langford A, Hofman MS, McJannett M, Martin AJ, Stockler MR, Davis ID; ENZA-p Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2024 May;25(5):563-571. doi: 10.1016/S1470-2045(24)00135-9. Epub 2024 Apr 12.

  PMID: 38621400 DERIVED

Related Links

• Description: Sponsor's website

MeSH Terms

Interventions

enzalutamide

Study Officials

• Louise Emmett, MBBS, FRACP

  St Vincent's Hospital, Sydney

  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

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 5, 2020
• Study Start: August 17, 2020
• Primary Completion: July 31, 2024
• Study Completion: January 1, 2025
• Last Updated: February 7, 2024

Record last verified: 2024-02

Locations

AU (15)