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Prostatic Neoplasms, Castration-ResistantPhase 4REDOSENCT03927391

Effect of a Reduced Dose Enzalutamide in Frail (m)CRPC Patients on Cognitive Side Effects

A Phase 4 study testing Enzalutamide in people with Prostatic Neoplasms, Castration-Resistant, run by Radboud University Medical Center at 3 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
3 sitesNetherlands
Study dates
30 May 2019to 8 Jan 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

3 sites in 1 country.

Netherlands3 sites

  • CWZ

    Nijmegen

  • Radboudumc

    Nijmegen

  • Franciscus Gasthuis en Vlietland hospital

    Rotterdam

Other trials in Netherlands

About this study

Official title: 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.

Being tested
Enzalutamide
Keywords
enzalutamide, cognitive side effects
Medical subject headings
Prostatic Neoplasms, Castration-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03927391
Study groupRoleWhat they receive
reference (normal) doseActive comparatorNormal dose of enzalutamide (160mg once daily)
Receives: Drug: Enzalutamide
test (reduced) doseExperimentalReduced dose of enzalutamide (120mg once daily)
Receives: Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    *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.

    Measured: 6 weeks

Secondary outcomes (7)

  1. 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.

    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.

    Measured: 12 weeks and 24 weeks

  2. 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).

    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.

    Measured: 6, 12 and 24 weeks

  3. 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).

    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.

    Measured: 6, 12 and 24 weeks

  4. 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).

    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.

    Measured: 6, 12 and 24 weeks

  5. To correlate exposure (Ctrough) of enzalutamide and n-desmethylenzalutamide to the CNS side effects.

    Correlations of Ctrough and CNS side effects

    Measured: 6, 12 and 24 weeks

  6. To determine the percentage (%) of subjects that remained on the allocated dose level until the end of the study.

    % subjects that without dose reductions or dose increments

    Measured: 6, 12 and 24 weeks

  7. To evaluate the effect of dose reduction on treatment efficacy according to prostate cancer working group 3 (PCWG3).

    Effect of dose reduction (120mg) on treatment efficacy

    Measured: 6, 12 and 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2019
  2. Study start30 May 2019
  3. Primary completion8 Jan 2024
  4. Study completion8 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Normal enzalutamide dose versus reduced dose in two patient groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03927391
Sponsor's protocol ID
REDOSE
Acronym
REDOSE
Status last verified
Jun 2024
First submitted
29 Mar 2019
Last updated
12 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Boerrigter E, Overbeek JK, Benoist GE, Somford DM, Hamberg P, Tol J, Scholtes B, Willemsen AECAB, Buffart LM, Kessels RPC, Mehra N, van Oort IM, van Erp NP. A Prospective Randomised Trial to Determine the Effect of a Reduced Versus Standard Dose of Enzalutamide on Side Effects in Frail Patients with Prostate Cancer. Eur Urol Oncol. 2024 Dec;7(6):1376-1383. doi: 10.1016/j.euo.2024.02.009. Epub 2024 Mar 13.

    PubMed 38485614

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Enzalutamide in people with Prostatic Neoplasms, Castration-Resistant, run by Radboud University Medical Center at 3 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03927391, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.

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