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Trial registered on ANZCTR


Registration number
ACTRN12619000567123
Ethics application status
Approved
Date submitted
1/11/2018
Date registered
11/04/2019
Date last updated
11/04/2019
Date data sharing statement initially provided
11/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
EnzAdapt: A clinical trial for men with prostate cancer that has spread, testing a new way of taking a standard medicine
Scientific title
EnzAdapt: Feasibility, acceptability and safety of adaptive dosing of enzalutamide in men with metastatic castrate-resistant prostate cancer
Secondary ID [1] 296494 0
EnzAdapt
Universal Trial Number (UTN)
U1111-1223-1401
Trial acronym
EnzAdapt
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 310277 0
castrate resistant prostate cancer 310278 0
Condition category
Condition code
Cancer 309012 309012 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Men treated with standard dose enzalutamide (4 x 40mg capsules po OD) for CRPC will be registered, and will be enrolled and enter trial procedures if they experience 50% or more decline of their PSA (i.e. the likely rare patient that experiences primary resistance will not be eligible to continue). When the PSA blood test falls by more than 50%, enzalutamide will then be stopped. Ongoing monthly reviews and PSA blood tests we be attended. The participant will be advised to re-initiate enzalutamide when the PSA level has reached the pre-treatment/baseline PSA level. E.g. if a man's PSA is 80 at the time of starting enzalutamide, falls below 40 and he paused enzalutamide treatment, then monthly visits and PSA blood tests will occur; when the man's blood test rises back to 80 or higher, he will be advised to restart the enzalutamide. This "loop" of patient-individualised precision adaptive therapy will be repeated for as long as there is ongoing patient consent, tolerance and safety (i.e. repeated re-response). Each time enzalutamide is stopped, it will be defined as the start of a new adaptive therapy cycle (a “loop”). This "loop" of patient-individualised precision adaptive therapy will be repeated indefinitely for as long as there is ongoing patient consent, tolerance and safety (i.e. repeated re-response). While the clinical trial will have a maximum of 24 months of follow-up for each participant, if the adaptive loops of therapy are continuing to control a participant's cancer after the end of follow-up for an individual participant, the participant and their clinician may choose to continue this strategy of dosing off-study.
Intervention code [1] 312815 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307967 0
1. Tolerability and acceptability of adaptively dosed enzalutamide will be defined as the number of men that are able to complete at least 3 adaptive loops of treatment divided by the number of men that are enrolled on study
Timepoint [1] 307967 0
The outcome of the study will be assessed at the time of the end of the third adaptive loop of treatment in the last patient enrolled on study
Secondary outcome [1] 353521 0
2. Safety as defined by adverse events (CTCAE v5.0)


Timepoint [1] 353521 0
2. Continuous during study treatment and for 30 days after the end of treatment
Secondary outcome [2] 369121 0
3. Efficacy of adaptively dose enzalutamide will be as defined as the frequency of PSA response/re-response after enzalutamide re-introduction in each loop; i.e the frequency of adaptive loops in each man on study where the PSA falls by 50%
Timepoint [2] 369121 0
3. PSA blood tests will be taken every month
Secondary outcome [3] 369122 0
4. Efficacy as defined by radiological response per PCWG3 criteria
Timepoint [3] 369122 0
4. Three monthly CT and bone scans until end of treatment or end of study
Secondary outcome [4] 369123 0
5. Efficacy as defined by median time to on-treatment failure on enzalutamide defined by PCWG3 criteria
Timepoint [4] 369123 0
5. At each treatment loop, each 3 monthly scan or at end of study

Eligibility
Key inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
· Histologically or biochemically confirmed adenocarcinoma of the prostate
· Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy (i.e., surgical or medical castration with testosterone at screening <0.5 ng/L)
o Patients who have not had a bilateral orchiectomy, must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial;
· Metastatic castration resistant prostate cancer (CRPC)
· Prior treatment with taxane chemotherapy, (e.g. docetaxel and/or cabazitaxel) or predicted to be intolerant and not eligible for future chemotherapy
· Controlled symptoms (opioids for cancer related pain stable for > 4 weeks, no need for urgent radiotherapy for symptomatic lesions)
· Metastatic disease defined as at least 1 documented metastatic lesion on either a whole body bone scan or a CT scan of the chest, abdomen and pelvis.
· Participant has chosen to take enzalutamide as standard of care treatment for CRPC
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
· Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
· Known or suspected brain metastasis or active leptomeningeal disease;
· Any other therapies for CRPC (excluding denosumab) to be discontinued 3 weeks prior to study.
· Prior treatments with CYP17 or androgen receptor inhibitors (abiraterone or enzalutamide prior to this course). Prior treatment with docetaxel or cabazitaxel is allowed.
· Documented liver metastases

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
The safety population will comprise all participants who received at least one administration of study medication. All safety analyses will be performed on the Safety Population. The analysis of safety data will be principally descriptive in nature. Adverse Events (AEs) and Serious Adverse Events (SAEs) will be tabulated by treatment allocation and CTCAE criteria including system organ class, term, and worst grade.
All efficacy analyses will be performed on the Safety Population. Efficacy analyses will be primarily descriptive for this safety and feasibility study. The primary efficacy analysis will measure PSA-progression free survival. Point estimates for time-to-event endpoints will estimated using the Kaplan-Meier method with appropriate confidence intervals. Kaplan-Meier curves will be produced to summarise the distribution of the time-to-event data.

Recruitment
Recruitment status
Not yet recruiting
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
Recruitment hospital [1] 12324 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 12325 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [3] 12326 0
Manning Rural Referral Hospital (Taree) - Taree
Recruitment postcode(s) [1] 24562 0
2298 - Waratah
Recruitment postcode(s) [2] 24563 0
2340 - Tamworth
Recruitment postcode(s) [3] 24564 0
2430 - Taree

Funding & Sponsors
Funding source category [1] 301078 0
Charities/Societies/Foundations
Name [1] 301078 0
Below the Belt Pedalthon
Address [1] 301078 0
http://www.belowthebelt.org.au/
ANZUP Cancer Trials Group Limited Registered Office
Lifehouse, Level 6, 119-143 Missenden Road,
Camperdown NSW 2050
Country [1] 301078 0
Australia
Funding source category [2] 301081 0
Other Collaborative groups
Name [2] 301081 0
ANZUP Cancer Trials Group
Address [2] 301081 0
119/143 Missenden Rd, Camperdown NSW 2050
Country [2] 301081 0
Australia
Primary sponsor type
Hospital
Name
Calvary Mater Newcastle
Address
Edith St, Waratah, NSW 2298
Country
Australia
Secondary sponsor category [1] 300691 0
None
Name [1] 300691 0
Address [1] 300691 0
Country [1] 300691 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301831 0
Hunter New England Local Health District Human Research Ethics Committee
Ethics committee address [1] 301831 0
Lookout Road
New Lambton NSW 2305
Postal address:
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 301831 0
Australia
Date submitted for ethics approval [1] 301831 0
05/10/2018
Approval date [1] 301831 0
31/10/2018
Ethics approval number [1] 301831 0
2018/PID00537

Summary
Brief summary
The purpose of this study is to test the idea of a new way of using an old drug in men with prostate cancer that has spread.

Who is it for?
You may be eligible for this study if you have advanced prostate cancer and are eligible to take a medicine called enzalutamide/Xtandi.

Study details
If a man taking enzalutamide chooses to take part in the study, their oncologist will advise them to pause taking their medication if their PSA blood test falls by over half. If their PSA blood test returns to pre-treatment levels, participants will then be advised to recommence taking the tablets again until again, the PSA blood test has decreased by more than 50%. The idea is to take breaks from the hormone tablets, using them for long enough to control the cancer, but then stopping and saving them up until later to treat the cancer again. The blood tests, scans, and doctors appointments in the trial are almost identical to normal treatments; men on the trial will be asked to complete short questionnaires, and have an extra blood test every three months.

It is hoped this study will demonstrate this strategy of treatment will reduce side-effects, and may improve the lives and survival of men with prostate cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88254 0
A/Prof Craig Gedye
Address 88254 0
Calvary Mater Newcastle, Edith St, Waratah, NSW 2298
Country 88254 0
Australia
Phone 88254 0
+61 2 4921 1211
Fax 88254 0
Email 88254 0
craig.gedye@calvarymater.org.au
Contact person for public queries
Name 88255 0
A/Prof Craig Gedye
Address 88255 0
Calvary Mater Newcastle, Edith St, Waratah, NSW 2298
Country 88255 0
Australia
Phone 88255 0
+61 2 4921 1211
Fax 88255 0
Email 88255 0
craig.gedye@calvarymater.org.au
Contact person for scientific queries
Name 88256 0
A/Prof Craig Gedye
Address 88256 0
Calvary Mater Newcastle, Edith St, Waratah, NSW 2298
Country 88256 0
Australia
Phone 88256 0
+61 2 4921 1211
Fax 88256 0
Email 88256 0
craig.gedye@calvarymater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Pilot study with small patient numbers
What supporting documents are/will be available?
No other documents available
Summary results
No Results