Evaluating Dose Timing (Morning vs Evening) of Endocrine-based Therapies in Metastatic Breast and Prostate Cancers

A Randomised, Multicentre Trial Evaluating the Dose Timing (Morning vs Evening) of Endocrine-based Therapies in Metastatic Breast and Prostate Cancers (REaCT-CHRONO-MetBP Pilot Study)

The REaCT-CHRONO-MetBP Pilot study will compare morning and evening administration of endocrine-based therapy in metastatic breast and prostate cancers.

Participants with metastatic breast or prostate cancer will be randomly placed in one of two groups: a morning group and an evening group. The group assignment will determine whether they take their endocrine therapy in the morning or the evening. The primary outcome of this pilot study is to evaluate the feasibility of study procedures in order to conduct a larger definitive trial in the future. The secondary outcomes include comparing quality of life, tolerability, and efficacy outcomes between the morning and evening groups for each of the two cancer cohorts (metastatic breast and prostate cancer).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Metastatic Prostate Cancer
• Intervention / Treatment: Other: Morning administration of CDK4/6 inhibitor; Other: Evening administration of CDK4/6 inhibitor; Other: Morning administration of ARPI; Other: Evening administration of ARPI

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lisa Vandermeer, MSc; Phone Number: 613-737-7700; Email: lvandermeer@ohri.ca
• Study Contact Backup: Name: Lauren Butterfield, MSc; Phone Number: 613-737-7700; Email: lbutterfield@ohri.ca

Study Locations

• Canada
  • Ontario
    • Kitchener, Ontario, Canada
      • Recruiting
      • Waterloo Regional Health Network
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital Cancer Centre
      • Contact: Lauren Butterfield, MSc; Phone Number: 613-737-7700; Email: lbutterfield@ohri.ca
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Not yet recruiting
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Cohort A (Breast Cohort) Inclusion Criteria

• Patients with metastatic hormonal receptor positive breast cancer
• Plan to receive endocrine therapy and a CDK4/6 inhibitor (either Ribociclib or Palbociclib) in the first-line metastatic setting
• Age ≥18 years
• Able to provide oral consent
• Willing and able to complete questionnaires as per study protocol

Cohort A (Breast Cohort) Exclusion Criteria

• Any contraindication in taking endocrine therapy and CDK4/6 inhibitor in the morning or evening
• Plan to receive abemaciclib (as this requires twice a day dosing)

Cohort B (Prostate Cancer) Inclusion Criteria

• Patients with metastatic castrate sensitive prostate cancer
• Plan to receive androgen receptor pathway inhibitor (either enzalutamide, apalutamide or abiraterone acetate) in combination with androgen deprivation therapy
• Age ≥18 years
• Able to provide oral consent
• Willing and able to complete questionnaires as per study protocol

Cohort B (Prostate Cancer) Exclusion Criteria

• Any contraindication in taking androgen receptor pathway inhibitor in the morning or evening
• Plan to receive darolutamide (as this requires twice a day dosing)
• Plan to receive docetaxel in combination with androgen receptor pathway inhibitor

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort A, Arm A: Breast Cancer Cohort, Morning Group; Participants with metastatic breast cancer in this arm are assigned morning administration of CDK4/6 inhibitor.	Other: Morning administration of CDK4/6 inhibitor; Morning administration of cyclin-dependent kinase (CDK) 4/6 inhibitor defined as, within one hour of the participant wake up time.
Active Comparator: Cohort A, Arm B: Breast Cancer Cohort, Evening Group; Participants with metastatic breast cancer in this arm are assigned evening administration of CDK4/6 inhibitor.	Other: Evening administration of CDK4/6 inhibitor; Evening administration of cyclin-dependent kinase (CDK) 4/6 inhibitor defined as, within one hour of the participant bedtime.
Active Comparator: Cohort B, Arm A: Prostate Cancer Cohort, Morning Group; Participants with metastatic prostate cancer in this arm are assigned morning administration of ARPI.	Other: Morning administration of ARPI; Morning administration of androgen receptor pathway inhibitors (ARPI) defined as, within one hour of the patient wake up time.
Active Comparator: Cohort B, Arm B: Prostate Cancer Cohort, Evening Group; Participants with metastatic prostate cancer in this arm are assigned evening administration of ARPI.	Other: Evening administration of ARPI; Evening administration of androgen receptor pathway inhibitors (ARPI) defined as, within one hour of the patient bedtime.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: accrual per site	Feasibility will be assessed according to a combination of metrics, including the accrual of at least 25 patients per cohort in one year for a total of three sites	1 year
Feasibility: participation rate	Feasibility will be assessed according to a combination of metrics, including participation rate of at least 60% among patients approached.	The accrual period, approximately 1 year
Feasibility: number of participants who received allocated intervention	Feasibility will be assessed according to a combination of metrics, including at least 80% of enrolled patients receive treatment as per their allocated intervention for at least 4 weeks.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life: Functional Assessment of Cancer Therapy-General	Health-related quality of life using Functional Assessment of Cancer Therapy-General (FACT-G). Cohort A and Cohort B will answer the FACT-G. FACT-G has a score range of 0 to 108. Higher scores indicate better quality of life.	Baseline and 4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: Functional Assessment of Cancer Therapy-Endocrine Symptoms	Health-related quality of life using Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES). Cohort A and Cohort B will answer the FACT-ES. FACT-ES has a score range of 0 to 184. Higher scores indicate better quality of life.	Baseline and 4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: Functional Assessment of Cancer Therapy-Breast	Health-related quality of life using Functional Assessment of Cancer Therapy-Breast (FACT-B). Cohort A will complete the FACT-B. FACT-B has a score range of 0 to 148. Higher scores indicate better quality of life.	Baseline and 4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Health-related quality of life: Functional Assessment of Cancer Therapy-Prostate	Health-related quality of life using Functional Assessment of Cancer Therapy-Prostate (FACT-P). Cohort B will complete the FACT-P. FACT-P has a score range of 0 to 156. Higher scores indicate better quality of life.	Baseline and 4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Number of changes in treatment dose		5 years
Number of treatment interruptions		5 years
Number of treatment discontinuations		5 years
Cohort A's adverse events of interest	The number of participants in Cohort A that experience QTc prolongation, neutropenia, febrile neutropenia, hepatobiliary function.	4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Cohort B's adverse events of interest	The number of participants in Cohort B that experience hypertension, hyperglycemia, rash, hypothyroidism, fatigue.	4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Adherence to treatment	Adherence to treatment measured by the Five-Item Medication Adherence Report Scale (MARS-5 score). The MARS-5 has a range of 5-25. Higher scores indicate high adherence.	4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Participant preference in dose timing	Participants rank their preference on a scale of 0 to 10, where 0=prefer to take treatment in the morning, 5=no preference, 10=prefer to take treatment in the evening.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to second-line systemic treatment	Time from the randomization to start of second-line systematic treatment. This is reported on the Health Care Provider (HCP) follow up questionnaire which is completed at the various timepoints outlined in the time frame.	4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years
Overall survival	Overall survival is the time from randomization to death from any cause. Survival status (yes/no) will be checked throughout the study at the various timepoints outlined in the time frame.	4-, 12-, 26-, 52-weeks, 2-years, 3-years, 4-years, 5-years, 6-years post-randomization.
PSA reduction at 6 months	Cohort B only: prostate-specific antigen reduction.	6 months

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Marie-France Savard, MD, The Ottawa Hospital; Principal Investigator: Ana-Alicia Beltran-Bless, MD, The Ottawa Hospital

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): February 2, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2033

Study Registration Dates

• First Submitted: September 18, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Actual): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; prostate cancer; metastatic cancer; Chronotherapy; endocrine therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Breast Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: REaCT-CHRONO-MetBP Pilot

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