- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03927391
Effect of a Reduced Dose Enzalutamide in Frail (m)CRPC Patients on Cognitive Side Effects (REDOSE)
March 26, 2023 updated by: Radboud University Medical Center
Effect of a Reduced Dose on Cognitive Side Effects of Enzalutamide in Frail (Metastatic) Castration-resistant Prostate Cancer Patients (REDOSE)
Prostate cancer is the most commonly diagnosed cancer among men in Western countries.
When the disease recurs as castration-resistant prostate cancer (CRPC) it is associated with a median overall survival of approximately 2 years with significant decrement in quality of life due to additional cancer-specific and treatment-induced morbidity.
Palliative agents currently used in the CRPC setting include the 2nd generation hormonal agents abiraterone acetate and enzalutamide but also radium-223, docetaxel and cabazitaxel.
Choices for treatment strategies are based on multiple factors such as age, co-morbidity and drug toxicity profile.
The side effect profile of enzalutamide is associated with central nervous system (CNS side effects) such as fatigue and depression.
The mechanism for these side effects is not yet fully understood, but it was shown in rodent studies that enzalutamide and its active metabolite penetrate into the CNS.
This might cause the CNS side effects that were later seen in the phase 1 study where fatigue was found to be a dose-dependent adverse event.
After dose reductions the symptoms resolved.
This was also found in a retrospective study of Japanese metastatic CRPC (mCRPC) patients (n=345) in which the side effects malaise and nausea decreased remarkably after dose reduction.
However, no exposure-response relation was observed in the study of Gibbons et al.
Additionally, based on the data of the phase 1 trial of enzalutamide it can be suggested that a minimum trough concentration of 5.0 mg/L could be considered as a target for exposure to enzalutamide.
In particular, frail (m)CRPC patients are more prone to develop CNS side effects on enzalutamide.
The investigator's hypothesis is that dose reduction to 75% (120mg) can be safely done to treat (m)CRPC in these patients with preserving optimal efficacy and less CNS side effects.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
50
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: n van Erp
- Phone Number: +31243610000
- Email: nielka.vanerp@radboudumc.nl
Study Locations
-
-
-
Nijmegen, Netherlands
- Radboudumc
-
Nijmegen, Netherlands
- CWZ
-
Rotterdam, Netherlands
- Franciscus Gasthuis en Vlietland hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Frailᵃ male patients with prostate cancer who will start treatment with enzalutamide within label
- Age at least 18 years
- Patient who are able and willing to give written informed consent prior to screening
- Patients from whom it is possible to collect blood samples
- Patients who are willing to answer the questionnaires and test
- Life expectancy of > 6 months
- Capable of understanding and answering Dutch tests and questionnaires, as determined by the investigator
ᵃ Frail is defined as:
- a score on the comprehensive G8 assessment with cut-off ≤14 points and
- score ≥grade 1 for Central Nervous Disorders according to the Common Toxicity Criteria Adverse Event (CTCAE) criteria, of one of the following: Fatigue, Concentration impairment, cognitive disturbance, amnesia, depressed level of consciousness, memory impairment, hypersomnia.
Exclusion Criteria:
- change in dose of opioids/sedatives/benzodiazepines during last 2 weeks before study)
- Use of psychostimulants such as methylphenidate within 1 week of start of study
- Diagnosed with medical conditions that affect cognition: Dementia, Alzheimer disease, Parkinson's disease, psychiatric disorders that affect cognition other than depression or anxiety complaints related to the disease
- Active infection or other comorbidities that may contribute to REDOSE, February 2019 Page 7 of 53 fatigue or cognition change within 4 weeks of study entry
- Clinical relevant anaemia
- MoCa score <20
- Hypersensitivity to the active substance or to any of the excipients.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: reference (normal) dose
Normal dose of enzalutamide (160mg once daily)
|
enzalutamide treatment
|
Experimental: test (reduced) dose
Reduced dose of enzalutamide (120mg once daily)
|
enzalutamide treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine the change in the CNS side effect fatigue* in frail (m)CRPC patients treated with a reduced dose of enzalutamide (120mg OD) compared to the standard dose of enzalutamide (160mg OD) after 6 weeks of treatment.
Time Frame: 6 weeks
|
*fatigue is measured by the self-reported FACIT-fatigue questionnaire version 4 (Dutch version).
Functional Assessment of Chronic Illness Therapy-Fatigue.
13-items are scored on a 5-point scale.
All items except items 7 (I have energy) and 8 (I am able to do my usual activities) are reverse-scored before item scores are summed to obtain a total score (range 0-52).
Higher scores reflect less fatigue.4
(Dutch version): Functional Assessment of Chronic Illness Therapy-Fatigue.
13-items are scored with a total score ranging 0-52.
Higher scores reflect less fatigue.
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine the decrease in the CNS side effect fatigue in frail (m)CRPC patients treated with a reduced dose of enzalutamide (120mg OD) compared to the standard dose of enzalutamide (160mg OD) after 12 weeks, and 24 weeks of treatment.
Time Frame: 12 weeks and 24 weeks
|
fatigue is measured by the self-reported FACIT-fatigue questionnaire version 4 (Dutch version).
Functional Assessment of Chronic Illness Therapy-Fatigue.
13-items are scored on a 5-point scale.
All items except items 7 (I have energy) and 8 (I am able to do my usual activities) are reverse-scored before item scores are summed to obtain a total score (range 0-52).
Higher scores reflect less fatigue.
|
12 weeks and 24 weeks
|
To determine the impact of cognition impairment in quality of life in frail (m)CRPC patients treated with a reduced dose of enzalutamide (120mg OD) compared to the standard dose of enzalutamide (160mg OD).
Time Frame: 6, 12 and 24 weeks
|
The impact of cognition impairment in quality of life is measured by the self-repored FACT-cog questionnaire.
FACT-cog: Functional Assessment of Cancer Therapy - For patients with Cognitive function issues.
There are 4 subscale scores (perceived cognitive impairments (range 0-72), impact of perceived cognitive impairments on quality of life (range 0-16), comments from others (range 0-16) and percieved cognitive abilities (range 0-28).
All subscale scores are summed to derive a total score.
The higher the score, the better quality of life.
|
6, 12 and 24 weeks
|
To determine cognition impairment in frail (m)CRPC patients treated with a reduced dose of enzalutamide (120mg OD) compared to the standard dose of enzalutamide (160mg OD).
Time Frame: 6, 12 and 24 weeks
|
cognition impairment is measured by the MoCA test.
Montreal Cognitive Assessment, is a test for cognition.
It covers 8 tasks: attention and concentration, executive functions, memory, language, visuospatial abilities, abstract thinking, calculating abilities and orientation.
The maximum score is 30 points.
The higher the score, the better the cognition is.
|
6, 12 and 24 weeks
|
To evaluate changes in depression score in frail (m)CRPC patients treated with a reduced dose of enzalutamide (120mg OD) compared to the standard dose of enzalutamide (160mg OD).
Time Frame: 6, 12 and 24 weeks
|
Geriatric depression scale 15 (GDS-15): 15 question using an ordinal score (yes/no).
Total score: maximum 15 points.
A score of 0 to 5 is normal.
A score greater than 5 suggests depression.
|
6, 12 and 24 weeks
|
To correlate exposure (Ctrough) of enzalutamide and n-desmethylenzalutamide to the CNS side effects.
Time Frame: 6, 12 and 24 weeks
|
Correlations of Ctrough and CNS side effects
|
6, 12 and 24 weeks
|
To determine the percentage (%) of subjects that remained on the allocated dose level until the end of the study.
Time Frame: 6, 12 and 24 weeks
|
% subjects that without dose reductions or dose increments
|
6, 12 and 24 weeks
|
To evaluate the effect of dose reduction on treatment efficacy according to prostate cancer working group 3 (PCWG3).
Time Frame: 6, 12 and 24 weeks
|
Effect of dose reduction (120mg) on treatment efficacy
|
6, 12 and 24 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 30, 2019
Primary Completion (Actual)
March 23, 2023
Study Completion (Anticipated)
August 1, 2023
Study Registration Dates
First Submitted
March 29, 2019
First Submitted That Met QC Criteria
April 23, 2019
First Posted (Actual)
April 25, 2019
Study Record Updates
Last Update Posted (Actual)
March 28, 2023
Last Update Submitted That Met QC Criteria
March 26, 2023
Last Verified
September 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- REDOSE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostatic Neoplasms, Castration-Resistant
-
University Hospital, GrenobleTerminatedCastration-resistant Prostate CancerFrance
-
Janssen Research & Development, LLCCompletedCastration-Resistant Prostatic NeoplasmsCanada, Belgium, United States, Spain, Netherlands, Italy, Russian Federation
-
Janux TherapeuticsRecruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | Castration Resistant Prostatic CancerUnited States, Australia
-
Australian and New Zealand Urogenital and Prostate...Peter MacCallum Cancer Centre, AustraliaRecruitingCastration Resistant Prostatic CancerAustralia
-
Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
-
Nuvation Bio Inc.WithdrawnProstate Cancer | Prostate Neoplasm | Cancer of the Prostate | Prostatic Cancer | Castrate Resistant Prostate Cancer | Cancer of Prostate | Castration Resistant Prostatic Cancer | Castration Resistant Prostatic NeoplasmsUnited States
-
British Columbia Cancer AgencySanofi; Ozmosis Research Inc.UnknownMetastatic Castration-Resistant Prostatic CancerCanada, Australia
-
Arcus Biosciences, Inc.Gilead SciencesActive, not recruitingProstatic Neoplasms, Castration-Resistant | Prostatic Cancer, Castration-Resistant | Castration Resistant Prostatic Neoplasms | Androgen-Resistant Prostatic NeoplasmsUnited States, Canada
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingProstate Cancer | Refractory Cancer | Castration Resistant Prostatic CancerUnited States
-
University of California, San FranciscoMerck Sharp & Dohme LLCCompletedMetastatic Prostate Cancer | Castration Resistant Prostatic CancerUnited States
Clinical Trials on Enzalutamide
-
ESSA PharmaceuticalsRecruitingProstate CancerCanada, United States, Australia
-
Astellas Pharma Europe B.V.Medivation, Inc.CompletedProstate Cancer | Pharmacokinetics of EnzalutamideUnited States
-
Groupe Hospitalier Pitie-SalpetriereCompletedEpilepsy | Prostate Cancer | Neuropathy | EncephalopathyFrance
-
Andreas JosefssonGöteborg University; Umeå University; Sahlgrenska University Hospital, Sweden; Sundsvall... and other collaboratorsTerminated
-
Hinova Pharmaceuticals Inc.CompletedMetastatic Castration Resistant Prostate CancerChina
-
Macquarie University, AustraliaUnknown
-
Fundación Canaria de Investigación SanitariaHospital Universitario de CanariasUnknown
-
Translational Research Center for Medical Innovation...Kagawa UniversityCompleted
-
National Cancer Institute (NCI)Terminated
-
Alessa Therapeutics Inc.National Cancer Institute (NCI)Not yet recruitingProstate AdenocarcinomaUnited States