Status:
ACTIVE_NOT_RECRUITING
Enzalutamide With Lu PSMA-617 Versus Enzalutamide Alone in Men With Metastatic Castration-resistant Prostate Cancer
Lead Sponsor:
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Collaborating Sponsors:
National Health and Medical Research Council, Clinical Trials Centre
Prostate Cancer Research Alliance
Conditions:
Metastatic Castration-Resistant Prostate Cancer
Eligibility:
MALE
18+ years
Phase:
PHASE2
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 ...
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 mon...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
August 17 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 1 2025
Estimated Enrollment :
162 Patients enrolled
Trial Details
Trial ID
NCT04419402
Start Date
August 17 2020
End Date
January 1 2025
Last Update
February 7 2024
Active Locations (15)
Enter a location and click search to find clinical trials sorted by distance.
1
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia, 2050
2
St Vincents Hospital
Darlinghurst, New South Wales, Australia, 2010
3
St George Hospital
Kogarah, New South Wales, Australia, 2217
4
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170