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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04419402


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04419402
Ethics application status
Date submitted
28/05/2020
Date registered
5/06/2020
Date last updated
7/02/2024

Titles & IDs
Public title
Enzalutamide With Lu PSMA-617 Versus Enzalutamide Alone in Men With Metastatic Castration-resistant Prostate Cancer
Scientific 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)
Secondary ID [1] 0 0
ANZUP 1901
Universal Trial Number (UTN)
Trial acronym
ENZA-p
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-Resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lu-PSMA
Treatment: Drugs - Enzalutamide

Experimental: 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.

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


Treatment: Drugs: Lu-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.

Treatment: Drugs: Enzalutamide
160 mg (four 40 mg capsules) daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Prostate Specific Antigen (PSA) Progression-Free Survival
Timepoint [1] 0 0
Date of randomisation to the date of first evidence of PSA progression - assessed up to study completion, approximately 4 years from recruitment.
Secondary outcome [1] 0 0
Radiographic Progression-Free Survival
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Prostate Specific Antigen (PSA) response rate
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Pain response and Progression-Free Survival
Timepoint [3] 0 0
Date of randomisation through study completion, approximately 4 years from start of recruitment
Secondary outcome [4] 0 0
Clinical Progression-Free Survival
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Aspects of Health-related Quality of life (HRQL)
Timepoint [5] 0 0
Assessed every 4-6 weeks, through study completion, approximately 4 years from recruitment.
Secondary outcome [6] 0 0
Frequency and Severity of Adverse Events
Timepoint [6] 0 0
Through study completion, approximately 4 years from recruitment.

Eligibility
Key inclusion criteria
1. 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
2. Castration-resistant prostate cancer (defined as disease progressing despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone agonist or antagonist).
3. 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.
4. 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)
5. Target or non-target lesions according to RECIST 1.1
6. 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)
7. ECOG performance status 0-2
8. Adequate renal function:

- Creatinine clearance = 40mL/ min
9. 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)
10. 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
11. Estimated life expectancy > 12 weeks
12. Study treatment both planned and able to start within 21 days of randomisation
13. Willing and able to comply with all study requirements (including both treatments: enzalutamide and Lu-PSMA), and all required study assessments
14. Signed, written, informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate
2. 68Ga-PSMA PET/CT SUVmax < 10 at a site of measurable disease > 10mm
3. Prior treatment with enzalutamide, darolutamide, or apalutamide. Prior treatment with abiraterone is allowed.
4. Prior treatment with any PSMA-targeted radiotherapy
5. Prior chemotherapy for mCRPC. Prior docetaxel in castration-sensitive setting is permitted
6. 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)
7. Concurrent illness, including severe infection that may jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety
8. 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
9. Men in sexual relationships with women of reproductive potential who are not willing/able to use medically acceptable forms of barrier contraception
10. History of:

1. seizure or any condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
2. loss of consciousness or transient ischemic attack within 12 months of randomization
3. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2025
Actual
Sample size
Target
Accrual to date
Final
162
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
St Vincents Hospital - Darlinghurst
Recruitment hospital [3] 0 0
St George Hospital - Kogarah
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [6] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [7] 0 0
Northern Cancer Institute - Sydney
Recruitment hospital [8] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [9] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 0 0
Monash Health - Clayton
Recruitment hospital [11] 0 0
Austin Health - Heidelberg
Recruitment hospital [12] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [13] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [14] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [15] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [6] 0 0
2298 - Newcastle
Recruitment postcode(s) [7] 0 0
2065 - Sydney
Recruitment postcode(s) [8] 0 0
4029 - Brisbane
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
3168 - Clayton
Recruitment postcode(s) [11] 0 0
3084 - Heidelberg
Recruitment postcode(s) [12] 0 0
3002 - Melbourne
Recruitment postcode(s) [13] 0 0
3004 - Melbourne
Recruitment postcode(s) [14] 0 0
6009 - Nedlands
Recruitment postcode(s) [15] 0 0
6150 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Clinical Trials Centre
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Prostate Cancer Research Alliance
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Endocyte
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/industry
Name [4] 0 0
Astellas Pharma Inc
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04419402
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Louise Emmett, MBBS, FRACP
Address 0 0
St Vincent's Hospital, Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04419402

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruiting in New Zealand
Province(s)/district(s)
Funding & Sponsors
Funding source category [1] 39
Charities/Societies/Foundations
Name [1] 39
Prostate Cancer Research Alliance (PCRA): An Australian Government and Movember Foundation Collaboration
Address [1] 39
Level 4, 21-31 Goodwood Street, Richmond, VIC, 3121
Country [1] 39
Australia
Funding source category [2] 40
Commercial sector/Industry
Name [2] 40
Endocyte
Address [2] 40
3000 Kent Ave Ste 1-100, West Lafayette, IN 47906
Country [2] 40
United States of America
Funding source category [3] 41
Commercial sector/Industry
Name [3] 41
Astellas Pharma Inc, Australia
Address [3] 41
Level 3, 6 Eden Park Drive, Macquarie Park New South Wales 2113
Country [3] 41
Australia
Primary sponsor
Other Collaborative groups
Primary sponsor name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Primary sponsor address
Lifehouse, Level 6, 119-143 Missenden Road,
Camperdown NSW 2050
Primary sponsor country
Australia
Other collaborator category [1] 37
University
Name [1] 37
National Health and Medical Research Council, Clinical Trials Centre
Address [1] 37
92-94 Parramatta Road Camperdown NSW 2050
Country [1] 37
Australia
Other collaborator category [2] 38
Government body
Name [2] 38
Australian Nuclear Science and Technology Organisation
Address [2] 38
New Illawarra Road, Lucas Heights NSW Australia
Country [2] 38
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 17
St Vincent's Hospital Human Research Ethics Committee
Address [1] 17
390 Victoria St, Darlinghurst NSW 2010
Country [1] 17
Australia
Date submitted for ethics approval [1] 17
Approval date [1] 17
28/05/2020
Ethics approval number [1] 17
 
Public notes

Contacts
Principal investigator
Title 173 0
A/Prof
Name 173 0
Louise Emmett, MBBS, FRACP
Address 173 0
St Vincent's Hospital, Sydney
Country 173 0
Australia
Phone 173 0
+61411331065
Fax 173 0
Email 173 0
[email protected]
Contact person for public queries
Title 174 0
Mrs
Name 174 0
Margaret McJannett
Address 174 0
Lifehouse, Level 6, 119-143 Missenden Road, Camperdown NSW 2050
Country 174 0
Australia
Phone 174 0
+61295625033
Fax 174 0
Email 174 0
[email protected]
Contact person for scientific queries
Title 175 0
A/Prof
Name 175 0
Louise Emmett, MBBS, FRACP
Address 175 0
St Vincent's Hospital, Sydney
Country 175 0
Australia
Phone 175 0
+61411331065
Fax 175 0
Email 175 0
[email protected]