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

  • STATUS
    Recruiting
  • End date
    Jun 1, 2023
  • participants needed
    160
  • sponsor
    Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Updated on 6 October 2021
renal function
carcinoma
direct bilirubin
metastasis
progressive disease
neutrophil count
liver metastases
bone scan
abiraterone
orchiectomy
bone metastases
enzalutamide
conjugated bilirubin
adenocarcinoma
pet/ct
prostate adenocarcinoma

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.

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).

Details
Condition Metastatic Castration Resistant Prostate Cancer
Treatment Enzalutamide, Lu-PSMA
Clinical Study IdentifierNCT04419402
SponsorAustralian and New Zealand Urogenital and Prostate Cancer Trials Group
Last Modified on6 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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)
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
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