Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Morning administration of endocrine therapy; Other: Evening administration of endocrine therapy

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 Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital Cancer Centre
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Metastatic cancer
• Previous endocrine therapy for breast cancer
• Plan to receive adjuvant abemaciclib

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morning administration of endocrine therapy; Administration of endocrine therapy defined as, within one hour of the patient wake up time	Other: Morning administration of endocrine therapy; Endocrine therapy administered within one hour of patient wake up time
Active Comparator: Evening administration of endocrine therapy; Administration of endocrine therapy defined as, within one hour of the patient bed time	Other: Evening administration of endocrine therapy; Endocrine therapy administered within one hour of the patient bed time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 12 weeks after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness	Incremental cost-effectiveness rations (cost per one quality-adjusted life year (QALY) gained).	52 weeks after treatment initiation
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.	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.	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)	52 weeks after treatment initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Non-compliance to Endocrine Therapy	Comparing rates of non-compliance and non-persistence to endocrine therapy with patient age, turmour stage, chemotherapy use and type of endocrine therapy. The rates of non-compliance and rates of non-persistence will be tracked throughout the duration of the study and then compared to patient age, tumour stage, chemotherapy use and the type of endocrine therapy used.	52 weeks after treatment initiation

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Marie-France Savard, MD, Ottawa Hospital Research Institute

Publications and helpful links

General 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.
• Savard 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.

Helpful Links

• The Rethinking Clinical Trials (REaCT) website

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): September 5, 2022
• Study Completion (Actual): July 29, 2023

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Endocrine Therapy; Chronotherapy; Chronotherapeutics
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: REaCT-CHRONO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No