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Metastatic Castration-Resistant Prostate CancerPhase 2ENZA-pNCT04419402

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

A Phase 2 study testing Lu-PSMA and Enzalutamide in people with Metastatic Castration-Resistant Prostate Cancer, run by Australian and New Zealand Urogenital and Prostate Cancer Trials Group at 15 sites in Australia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Lu-PSMA and Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
15 sitesAustralia
Study dates
17 Aug 2020to 1 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 32Show fewer
  • 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
  • Prior treatment with abiraterone * Based on conventional imaging (CT and/or bone scan)
  • Target or non-target lesions according to RECIST 1.1
  • Significant PSMA avidity on 68Ga-PSMA PET/CT, defined as SUVmax >15 at a single site (regardless of lesion size) and SUV max >10 at sites of disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact)
  • ECOG performance status 0-2
  • Adequate renal function:
  • Creatinine clearance ≥ 40mL/ min
  • Adequate liver function:
  • Bilirubin < 1.5 x upper limit of normal (ULN) (or if bilirubin is between 1.5 - 2x ULN, must have a normal conjugated bilirubin)
  • AST or ALT ≤ 2.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases)
  • Adequate bone marrow function:
  • Platelets ≥ 100 x109/L
  • Haemoglobin ≥ 90g/L (no red blood cell transfusion in last 4 weeks)
  • Neutrophils > 1.5 x109/L
  • Estimated life expectancy > 12 weeks
  • Study treatment both planned and able to start within 21 days of randomisation
  • Willing and able to comply with all study requirements (including both treatments: enzalutamide and Lu-PSMA), and all required study assessments
  • Signed, written, informed consent

Who cannot join

  • Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate
  • 68Ga-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)
Show all 13Show fewer
  • 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

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Australia15 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland, 4029

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • Monash Health

    Clayton, Victoria, 3168

  • St Vincents Hospital

    Darlinghurst, New South Wales, 2010

  • Austin Health

    Heidelberg, Victoria, 3084

  • St George Hospital

    Kogarah, New South Wales, 2217

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Macquarie University Hospital

    Macquarie Park, New South Wales, 2109

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3002

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Calvary Mater Newcastle

    Newcastle, New South Wales, 2298

  • Fiona Stanley Hospital

    Perth, Western Australia, 6150

  • Northern Cancer Institute

    Sydney, New South Wales, 2065

Other trials in Australia

About this study

Official title: ENZA-p: A Randomised Phase II Trial Using PSMA as a Therapeutic Agent and Prognostic Indicator in Men With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide (ANZUP 1901)

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.

Read the detailed description

This is an open label, randomised, stratified, 2-arm, multicentre phase 2 clinical trial recruiting 160 participants over 12 months and followed until 150 events occurred (approximately another 18 months). Participants will be randomised to enzalutamide or enzalutamide and Lu-PSMA in a 1:1 ratio. A minimisation approach will be used to minimise chance imbalances across the following stratification factors: study site, volume of disease (>20 versus ≤20 sites of disease measured on 68Ga-PSMA PET/CT), prior treatment with early docetaxel for castration- sensitive disease (yes vs no), and prior treatment with early abiraterone for castration-sensitive disease (yes vs no).

Being tested
Lu-PSMA, Enzalutamide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lu-PSMADrug

    Also called 177Lutetium -PSMA 617 also referred to as 177Lu-PSMA

    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.

  • EnzalutamideDrug

    Also called Xtandi

    160 mg (four 40 mg capsules) daily.

Study groups in NCT04419402
Study groupRoleWhat they receive
Lu-PSMA + EnzalutamideExperimentalLu-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.
Receives: Drug: Lu-PSMA; Drug: Enzalutamide
EnzalutamideActive comparatorEnzalutamide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.
Receives: Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Radiographic Progression-Free Survival

    Radiographic progression-free survival is defined as the interval from the date of randomisation to the date of first evidence of radiographic progression on imaging, or the date of last known follow-up without progression.

    Measured: 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.

  2. Prostate Specific Antigen (PSA) response rate

    PSA response rate is defined as the proportion of participants in each group with a PSA reduction of 50% or more from baseline.

    Measured: 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

  3. Pain response and Progression-Free Survival

    Pain is measured using the McGill-Melzack Present Pain Intensity scale (PPI). Pain Response is defined as a reduction of 2 or more points for participants with a baseline PPI score of 2 or more. Pain progression is defined as and an increase of 1 or more points in the nadir PPI score.

    Pain Response is defined as a reduction of 2 or more points for participants with a baseline PPI score of 2 or more.

    Pain progression is defined as and an increase of 1 or more points in the nadir PPI score.

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

  4. Clinical Progression-Free Survival

    Clinical progression is defined by progression on imaging, development of symptoms attributable to cancer progression, the need for radiotherapy to new metastases or initiation of other anticancer treatment for prostate cancer.

    Measured: 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.

  5. Aspects of Health-related Quality of life (HRQL)

    The European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire includes five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), and a global health and quality-of-life scale to assess HRQL in cancer patients. The Patient DATA form is a simple, multi-item quality of life instrument based on 11-point numeric rating scales for a range of relevant symptoms and functions. It combines cancer specific items from the UBQ-C, GLQ-8 and LASA cancer-specific quality of life instruments. The Fear of Cancer Progression form is a short questionnaire assessing possible future concerns related to the participant's illness.

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

  6. Frequency and Severity of Adverse Events

    The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 will be used to classify and grade the intensity of adverse events during study treatment.

    Measured: Through study completion, approximately 4 years from recruitment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2020
  2. Study start17 Aug 2020
  3. Primary completion12 Apr 2024
  4. Study completion1 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
162 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04419402
Sponsor's protocol ID
ANZUP 1901
Acronym
ENZA-p
Status last verified
Jun 2026
First submitted
28 May 2020
Last updated
22 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ayati N, Papa N, Crumbaker M, Subramaniam S, Joshua AM, Alipour R, Iravani A, Askari E, Khan S, Yadav S, Eiber M, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Nguyen A, Hofman MS, Sandhu S, Hioki T, van Oorschodt JCJ, Devitt K, Willowson K, Sharma S, Stancu A, Chauvie S, Wilson P, Martin AJ, Thomas H, Stockler MR, Davis ID, Emmett L; Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. 177Lu-PSMA-617 SPECT/CT for Early Prediction of Overall Survival in Participants with Metastatic Castration-Resistant Prostate Cancer. Radiology. 2026 Apr;319(1):e252672. doi: 10.1148/radiol.252672.

    PubMed 42048586

  • Emmett L, Swiha M, Papa N, Subramaniam S, Crumbaker M, Joshua AM, Nguyen A, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Pathmanandavel S, Hope T, Ayati N, Hofman MS, Sandhu S, Niu C, Martin AJ, Thomas H, Stockler MR, Davis ID; Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. Predictive value of early PSMA upregulation for the response to enzalutamide +/- 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer: substudy of the randomized, phase 2 ENZA-p trial. Nat Cancer. 2026 Apr;7(4):622-630. doi: 10.1038/s43018-026-01140-3. Epub 2026 Apr 15.

    PubMed 41986500

  • Emmett L, Papa N, Sartor O, Morris MJ, Subramaniam S, Crumbaker M, Ayati N, Chen J, Herrmann K, Gafita A, Swiha M, Joshua AM, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Ho B, Khan S, Tan TH, Bills M, Nguyen A, Thein T, Sidhom G, Wong K, Martin AJ, Hofman MS, Sandhu S, Thomas H, Stockler MR, Davis ID; ENZA-p Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Prognostic Value of Interim PSMA-PET Total Tumor Volume for Overall Survival Within ENZA-p, A Randomized Phase 2 Trial of Enzalutamide Versus Enzalutamide Plus [177Lu] Lu-PSMA-617 (ANZUP1901). Eur Urol. 2026 Apr 8:S0302-2838(26)02063-4. doi: 10.1016/j.eururo.2026.03.026. Online ahead of print.

    PubMed 41956861

  • 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.

    PubMed 40752515

  • 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.

    PubMed 39956124

  • 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.

    PubMed 38621400

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lu-PSMA and Enzalutamide in people with Metastatic Castration-Resistant Prostate Cancer, run by Australian and New Zealand Urogenital and Prostate Cancer Trials Group at 15 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prostate Specific Antigen (PSA) Progression-Free Survival (time frame: Date of randomisation to the date of first evidence of PSA progression - assessed up to study completion, approximately 4 years from recruitment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04419402, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.

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