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)
Overview
- Phase
- Phase 2
- Intervention
- Lu-PSMA
- Conditions
- Metastatic Castration-Resistant Prostate Cancer
- Sponsor
- Australian and New Zealand Urogenital and Prostate Cancer Trials Group
- Enrollment
- 162
- Locations
- 15
- Primary Endpoint
- Prostate Specific Antigen (PSA) Progression-Free Survival
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
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.
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).
Investigators
Eligibility Criteria
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 \*
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:
Arms & Interventions
Lu-PSMA + Enzalutamide
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.
Intervention: Lu-PSMA
Lu-PSMA + Enzalutamide
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.
Intervention: Enzalutamide
Enzalutamide
Enzalutamide - 160 mg (four 40 mg capsules): daily until participant is no longer clinically benefiting, or experiences unacceptable toxicity.
Intervention: Enzalutamide
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- 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.)
- 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.)
- Frequency and Severity of Adverse Events(Through study completion, approximately 4 years from 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)
- Aspects of Health-related Quality of life (HRQL)(Assessed every 4-6 weeks, through study completion, approximately 4 years from recruitment.)