Breast CancerPhase 4NCT04864405
Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance
A Phase 4 study testing Morning administration of endocrine therapy and Evening administration of endocrine therapy in people with Breast Cancer, run by Ottawa Hospital Research Institute at 2 sites in Canada.
Trial summary
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Morning administration of endocrine therapy and Evening administration of endocrine therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 245 participants
- Where
- 2 sitesCanada
- Study dates
- 30 Jun 2021to 29 Jul 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with an early stage or locally advanced hormonal receptor positive breast cancer
- Plan to receive endocrine therapy
- 18 years of age or older
- Able to provide oral consent
- Willing and able to complete questionnaires as per study protocol
Who cannot join
- Metastatic cancer
- Previous endocrine therapy for breast cancer
- Plan to receive adjuvant abemaciclib
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
The Ottawa Hospital Cancer Centre
Ottawa, Ontario
Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, P7B 6V4
About this study
Official title: A Pragmatic Randomised, Multicentre Trial Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance (REaCT-CHRONO)
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Chronotherapy, also called chronotherapeutics, is defined as the administration of a medication in coordination with circadian rhythm in order to minimize side effects and yield a greater efficacy. The investigators propose to perform a pragmatic, multi-centre, open-label, randomized clinical trial to establish the optimal timing (morning vs. evening) of administering endocrine therapy based on side effects and benefits in early stage breast cancer patients.
Read the detailed description
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Compliance is defined as the degree or extent of conformity to the recommended administration by the provider, whereas persistence refers to the act of continuing treatment for a certain prescribed duration. Treatment adherence is especially important in breast cancer, as early cessation or reduced compliance to hormonal therapy are associated with reduced disease-free survival and increased mortality. Chronotherapy, also called chronotherapeutics, is defined as the administration of a medication in coordination with circadian rhythm in order to minimize side effects and yield a greater efficacy. The investigators propose to perform a pragmatic, multi-centre, open-label, randomized clinical trial to establish the optimal timing (morning vs. evening) of administering endocrine therapy based on side effects and benefits in early stage breast cancer patients.
- Conditions
- Breast Cancer
- Being tested
- Morning administration of endocrine therapy, Evening administration of endocrine therapy
- Keywords
- Breast Cancer, Endocrine Therapy, Chronotherapy, Chronotherapeutics
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Morning administration of endocrine therapyOther
Endocrine therapy administered within one hour of patient wake up time
Evening administration of endocrine therapyOther
Endocrine therapy administered within one hour of the patient bed time
| Study group | Role | What they receive |
|---|---|---|
| Morning administration of endocrine therapy | Active comparator | Administration of endocrine therapy defined as, within one hour of the patient wake up time Receives: Other: Morning administration of endocrine therapy |
| Evening administration of endocrine therapy | Active comparator | Administration of endocrine therapy defined as, within one hour of the patient bed time Receives: Other: Evening administration of endocrine therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Endocrine Toxicity and Tolerability at 12 Weeks
Measured by the change in total Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire from baseline to 12 weeks following the beginning of endocrine therapy. FACT-ES is a validated sub scale of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total range of 0 to 184. Higher FACT-ES scores indicate better outcomes. The current outcome is a change in FACT-ES scores.
Measured: Baseline to 12 weeks after treatment initiation
Secondary outcomes (4)
Change in Endocrine Toxicity and Tolerability
Measured by the change in total score and individual Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaires from baseline to 4, 8, 12 and 52 weeks following the beginning of endocrine therapy. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total score range of 0 to 184. Higher scores indicate better quality of life. The current outcome is a change in FACT-ES scores over time.
Measured: Baseline, 4, 8, 12 and 52 weeks after treatment initiation
Change in Health Related Quality of Life Scores
Measured by the change in the total score and individual sub scales of the validated Functional Assessment of Cancer Therapy for patients with Breast cancer (FACT-B) questionnaire from baseline to 4, 8, 12 and 52 weeks following the beginning of endocrine therapy. The FACT-B consists of 37 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total score range of 0 to 148. Higher FACT-B scores indicate better quality of life. The current outcome is a change in FACT-B scores over time.
Measured: Baseline, 4, 8, 12 and 52 weeks after treatment initiation
Number of Participants Who Were Compliant With ET
Rates of non-persistence or non-compliance with initially prescribed endocrine therapy (ET)
Measured: 52 weeks after treatment initiation
Cost-effectiveness
Incremental cost-effectiveness rations (cost per one quality-adjusted life year (QALY) gained).
Measured: 52 weeks after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start30 Jun 2021
- Primary completion5 Sep 2022
- Study completion29 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 245 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie-France Savard, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04864405
- Sponsor's protocol ID
- REaCT-CHRONO
- Status last verified
- Dec 2025
- First submitted
- 9 Apr 2021
- Last updated
- 8 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Beltran-Bless AA, Vandermeer L, Ibrahim MFK, Hutton B, Shorr R, Savard MF, Clemons M. Does the Time of Day at Which Endocrine Therapy Is Taken Affect Breast Cancer Patient Outcomes? Curr Oncol. 2021 Jul 6;28(4):2523-2528. doi: 10.3390/curroncol28040229.
PubMed 34287262Savard MF, Ibrahim M, Saunders D, Pond GR, Ng TL, Awan AA, Sehdev S, Alqahtani N, Vandermeer L, MacDonald F, Beltran-Bless AA, Fallowfield L, Clemons M. A pragmatic, multicenter, randomized trial comparing morning versus evening dosing of adjuvant endocrine therapy (REaCT-CHRONO Study). NPJ Breast Cancer. 2025 May 29;11(1):49. doi: 10.1038/s41523-025-00762-7.
PubMed 40442096
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic Randomised, Multicentre Trial Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance (REaCT-CHRONO)
- ClinicalTrials.gov ID
- NCT04864405
- Acronym / sponsor ID
- REaCT-CHRONO
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Endocrine Therapy, Chronotherapy, Chronotherapeutics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 245 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 30 Jun 2021 (actual)
- Primary completion
- 5 Sep 2022 (actual)
- Study completion
- 29 Jul 2023 (actual)
- First posted
- 28 Apr 2021 (actual)
- Results
- Posted 8 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Chronotherapy, also called chronotherapeutics, is defined as the administration of a medication in coordination with circadian rhythm in order to minimize side effects and yield a greater efficacy. The investigators propose to perform a pragmatic, multi-centre, open-label, randomized clinical trial to establish the optimal timing (morning vs. evening) of administering endocrine therapy based on side effects and benefits in early stage breast cancer patients.
Detailed description
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Compliance is defined as the degree or extent of conformity to the recommended administration by the provider, whereas persistence refers to the act of continuing treatment for a certain prescribed duration. Treatment adherence is especially important in breast cancer, as early cessation or reduced compliance to hormonal therapy are associated with reduced disease-free survival and increased mortality. Chronotherapy, also called chronotherapeutics, is defined as the administration of a medication in coordination with circadian rhythm in order to minimize side effects and yield a greater efficacy. The investigators propose to perform a pragmatic, multi-centre, open-label, randomized clinical trial to establish the optimal timing (morning vs. evening) of administering endocrine therapy based on side effects and benefits in early stage breast cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morning administration of endocrine therapy | Active comparator | Other: Morning administration of endocrine therapyAdministration of endocrine therapy defined as, within one hour of the patient wake up time |
| Evening administration of endocrine therapy | Active comparator | Other: Evening administration of endocrine therapyAdministration of endocrine therapy defined as, within one hour of the patient bed time |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with an early stage or locally advanced hormonal receptor positive breast cancer
- Plan to receive endocrine therapy
- 18 years of age or older
- Able to provide oral consent
- Willing and able to complete questionnaires as per study protocol
Key exclusion criteria (3 listed)
- Metastatic cancer
- Previous endocrine therapy for breast cancer
- Plan to receive adjuvant abemaciclib
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Morning administration of endocrine therapyEndocrine therapy administered within one hour of patient wake up time | Other | Morning administration of endocrine therapy |
| Evening administration of endocrine therapyEndocrine therapy administered within one hour of the patient bed time | Other | Evening administration of endocrine therapy |
Primary outcome
Change in Endocrine Toxicity and Tolerability at 12 Weeks
Time frame: Baseline to 12 weeks after treatment initiation
Measured by the change in total Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire from baseline to 12 weeks following the beginning of endocrine therapy. FACT-ES is a validated sub scale of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total range of 0 to 184. Higher FACT-ES scores indicate better outcomes. The current outcome is a change in FACT-ES scores.
4 secondary outcomes
Change in Endocrine Toxicity and Tolerability
Time frame: Baseline, 4, 8, 12 and 52 weeks after treatment initiation
Change in Health Related Quality of Life Scores
Time frame: Baseline, 4, 8, 12 and 52 weeks after treatment initiation
Number of Participants Who Were Compliant With ET
Time frame: 52 weeks after treatment initiation
Cost-effectiveness
Time frame: 52 weeks after treatment initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34287262Beltran-Bless AA, Vandermeer L, Ibrahim MFK, Hutton B, Shorr R, Savard MF, Clemons M. Does the Time of Day at Which Endocrine Therapy Is Taken Affect Breast Cancer Patient Outcomes? Curr Oncol. 2021 Jul 6;28(4):2523-2528. doi: 10.3390/curroncol28040229.
- Results publication: PubMed 40442096Savard MF, Ibrahim M, Saunders D, Pond GR, Ng TL, Awan AA, Sehdev S, Alqahtani N, Vandermeer L, MacDonald F, Beltran-Bless AA, Fallowfield L, Clemons M. A pragmatic, multicenter, randomized trial comparing morning versus evening dosing of adjuvant endocrine therapy (REaCT-CHRONO Study). NPJ Breast Cancer. 2025 May 29;11(1):49. doi: 10.1038/s41523-025-00762-7.
- The Rethinking Clinical Trials (REaCT) websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie-France Savard, MD principal investigator
Ottawa Hospital Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morning administration of endocrine therapy and Evening administration of endocrine therapy in people with Breast Cancer, run by Ottawa Hospital Research Institute at 2 sites in Canada.
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 5 inclusion and 3 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 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
Yes. Results are posted in the registry (first posted 8 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Endocrine Toxicity and Tolerability at 12 Weeks (time frame: Baseline to 12 weeks after treatment initiation). 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 NCT04864405, which also lists 2 linked publications.
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 8 Jan 2026.