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

NCT04864405 | Completed Phase 4 Results

• 1 other identifier: REaCT-CHRONO
• Study Type: interventional
• Target: 245
• Locations: 1 country
• Sites: 2

Brief 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. 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

Keywords

Breast Cancer; Endocrine Therapy; Chronotherapy; Chronotherapeutics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in Endocrine Toxicity and Tolerability

  Baseline, 4, 8, 12 and 52 weeks after treatment initiation

• Change in Health Related Quality of Life Scores

  Baseline, 4, 8, 12 and 52 weeks after treatment initiation

• Number of Participants Who Were Compliant With ET

  52 weeks after treatment initiation

• Cost-effectiveness

  52 weeks after treatment initiation

Other Outcomes (1)

• Rates of Non-compliance to Endocrine Therapy

  52 weeks after treatment initiation

Study Arms (2)

Morning administration of endocrine therapy

ACTIVE COMPARATOR

Administration of endocrine therapy defined as, within one hour of the patient wake up time

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

Other: Evening administration of endocrine therapy

Interventions

Morning administration of endocrine therapy OTHER

Endocrine therapy administered within one hour of patient wake up time

Morning administration of endocrine therapy

Evening administration of endocrine therapy OTHER

Endocrine therapy administered within one hour of the patient bed time

Evening administration of endocrine therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with an early stage or locally advanced hormonal receptor positive breast cancer
• Plan to receive endocrine therapy
• years of age or older
• Able to provide oral consent
• Willing and able to complete questionnaires as per study protocol

You may not qualify if:

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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (2)

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Related Publications (2)

• 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.

  PMID: 34287262 BACKGROUND

• 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.

  PMID: 40442096 RESULT

Related Links

• The Rethinking Clinical Trials (REaCT) website

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Marie-France Savard, MD
• Organization: The Ottawa Hospital Cancer Centre

msavard@toh.ca

613-737-7700

Study Officials

• Marie-France Savard, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 28, 2021
• Study Start: June 30, 2021
• Primary Completion: September 5, 2022
• Study Completion: July 29, 2023
• Last Updated: January 8, 2026
• Results First Posted: January 8, 2026

Record last verified: 2025-12

Locations

CA (2)