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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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
5/10/2020

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 - 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.
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 - 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.
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 - PSA response rate is defined as the proportion of participants in each group with a PSA reduction of 50% or more from baseline.
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 - 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.
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 - 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.
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) - 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.
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 - 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.
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 = 10 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

- Early abiraterone for castration-sensitive prostate cancer * 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
Gender
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 new androgen signalling targeted agents (e.g. enzalutamide,
darolutamide, or apalutamide). Prior therapy with abiraterone is permitted only in the
castration -sensitive setting

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3002 - Melbourne

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/show/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
Margaret McJannett
Address 0 0
Country 0 0
Phone 0 0
+6129562 5033
Fax 0 0
Email 0 0
trials@anzup.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/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
emmetthruby@gmail.com
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
margaret@anzup.org.au
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
emmetthruby@gmail.com