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Trial registered on ANZCTR


Registration number
ACTRN12617000616370
Ethics application status
Approved
Date submitted
13/04/2017
Date registered
1/05/2017
Date last updated
2/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of enzalutamide dose reduction on fatigue, cognition, and drug trough levels in patients with prostate cancer
Scientific title
Effect of enzalutamide dose reduction on fatigue, cognition, and drug trough levels in patients with prostate cancer
Secondary ID [1] 291548 0
HGMQ201502
Secondary ID [2] 291829 0
NCT03124615
Universal Trial Number (UTN)
Trial acronym
EFFECT study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 302738 0
Condition category
Condition code
Cancer 302253 302253 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be receiving standard dose enzalutamide (160mg daily) as determined by treating physician until disease progression or intolerance

If the patient experiences a greater than or equal to Grade 3 toxicity (as per CTCAE guidelines) withhold enzalutamide for one week or until symptoms improve to at least Grade 2, then resume at the same or a reduced dose (120 mg or 80 mg) at the discretion of the investigator

Fatigue and cognition are assessed once every 4-8 weeks for the duration of treatment depending on stability of dosage

Dose reduction will be undertaken in 40mg increments, depending on level of cognition and fatigue impairment at the discretion of the investigator or ceased altogether

Intervention adherence will not be formally assessed in this study
Patients will be followed up for 12 months for the purposes of this study
Intervention code [1] 297688 0
Treatment: Drugs
Comparator / control treatment
No Control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301762 0
Determine the proportion of patients who have an improvement in cognition & fatigue symptoms. (Composite Primary Outcome, Questionnaire was designed for this study to assess their cognition & fatigue after dose reduction, with improvement considered as patients clearly choosing the option 'Better')
Timepoint [1] 301762 0
One year post enrolment
Primary outcome [2] 301763 0
Determine the median total trough level (enzalutamide + N-desmethyl enzalutamide) via plasma assay (Composite)
Timepoint [2] 301763 0
Blood samples are to be taken every 4 weeks for 2 months post dose reduction (if the patient has a Grade 3 fatigue or cognition change and if the Investigator attributes toxicity to enzalutamide)
If for the duration of treatment, no dose reductions are made, blood samples will not be required
Secondary outcome [1] 333793 0
Total trough level (Enzalutamide + N-desmethyl enzalutamide) level before and after dose reduction via plasma assay (Composite)
Timepoint [1] 333793 0
Blood samples are to be taken every 4 weeks for 2 months post dose reduction (if the patient has a Grade 3 fatigue or cognition change and if the Investigator attributes toxicity to enzalutamide)
If for the duration of treatment, no dose reductions are made, blood samples will not be required
Secondary outcome [2] 333794 0
Changes in serum PSA level in patients undergoing dose reduction of enzalutamide (via a blood test)
Timepoint [2] 333794 0
Assessed once every 3 months for the duration of treatment

Eligibility
Key inclusion criteria
1. Patients with prostate cancer who have commenced enzalutamide within 3 months
2. Patient must have concomitant LHRH agonist or antagonist (no single agent enzalutamide)
3. Receiving enzalutamide before or after docetaxel
4. Patients may have hormone-sensitive or castrate resistant disease
5. Patients may have metastatic (M1) or non-metastatic (M0) disease
6. Onset of grade 3 or more cognition change and/or fatigue after commencement of enzalutamide considered to be due to enzalutamide
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinical dementia
2. Concomitant use of drugs known to impair cognition such as benzodiazepines or antihistamines.
3. Concomitant use of strong CYP3A4 and/ or CYP2C8 inducers or inhibitors.
4. Patient expected to have a change in opioid dose during the study period or have had a change 4 weeks before study entry.
5. Diagnosed with sleep apnoea
6. Brain metastases, prior seizures, drugs that significantly reduce seizure threshold.
7. Active infection or other intercurrent illness that may contribute to fatigue or cognition change within 4 weeks of study entry.

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)
N/A
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
N/A
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: 47 patients
Justification: The primary endpoint is an improvement in the fatigue and cognition symptoms. Improvement will be defined as the patient answering ‘Better’ in the cognition/ fatigue question at the lowest dose of enzalutamide.
For the dose reduction manoeuvre to be clinically useful, we expect the rate of improvement to be 80% or better. As improvement of 60% or less would be considered clinically marginal, a sample size of 43 patients will have 80% power with 95% confidence to exclude a 60% improvement rate in favour of a more meaningful 80% improvement (Simon design). If a patient drops out due to fatigue or cognition side effects they will be recorded as a failure to the dose reduction manoeuvre. If the patient drops out for any other reason (eg progression of cancer) then they will be regarded as not evaluable. Assuming a 10% drop out rate due to disease progression or other non-fatigue/ cognition score gives a total study number of 47 patients
The patient-reported symptoms will also be validated compared with the validated questionnaires (Brief Fatigue Inventory; Trail making tests A and B; Hopkins Verbal Learning Test – Revised; Controlled Oral Word Association Test).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/05/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
47
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 15779 0
2109 - Macquarie University

Funding & Sponsors
Funding source category [1] 296036 0
Commercial sector/Industry
Name [1] 296036 0
Astellas Pharma
Country [1] 296036 0
Australia
Primary sponsor type
University
Name
Macquarie University
Address
Macquarie University
Balaclava Road, New South Wales, 2109
Country
Australia
Secondary sponsor category [1] 295102 0
None
Name [1] 295102 0
Address [1] 295102 0
Country [1] 295102 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297295 0
Macquarie University Human Research Ethics Committee (Medical Sciences)
Ethics committee address [1] 297295 0
Ethics committee country [1] 297295 0
Date submitted for ethics approval [1] 297295 0
24/01/2017
Approval date [1] 297295 0
23/03/2017
Ethics approval number [1] 297295 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73614 0
Prof Howard Gurney
Address 73614 0
Suite 407, Level 4, Department of Clinical Medicine Building F10A 2 Technology Place Macquarie University, NSW 2109
Country 73614 0
Australia
Phone 73614 0
+61 (0)2 98123526
Fax 73614 0
+61 (0)2 98123533
Email 73614 0
[email protected]
Contact person for public queries
Name 73615 0
Radhika Butala
Address 73615 0
Suite 407, Level 4, Department of Clinical Medicine Building F10A
2 Technology Place
Macquarie University, NSW 2109
Country 73615 0
Australia
Phone 73615 0
+61 (0)2 98123561
Fax 73615 0
+61 (0)2 98123533
Email 73615 0
[email protected]
Contact person for scientific queries
Name 73616 0
Howard Gurney
Address 73616 0
Suite 407, Level 4, Department of Clinical Medicine Building F10A
2 Technology Place
Macquarie University, NSW 2109
Country 73616 0
Australia
Phone 73616 0
+61 (0)2 98123526
Fax 73616 0
+61 (0)2 98123533
Email 73616 0
[email protected]

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