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

Study Overview
=================
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.

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.

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)

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Other: Morning administration of endocrine therapy
* Other: Evening administration of endocrine therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). It is designed to measure five domains of health related quality of life in breast cancer patients receiving endocrine therapy: physical, social, emotional, functional well-being as well as an endocrine symptom sub-scale (ESS). | 12 weeks after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). It is designed to measure five domains of health related quality of life in breast cancer patients receiving endocrine therapy: physical, social, emotional, functional well-being as well as an endocrine symptom sub-scale (ESS). | Baseline, 4, 8, 12 and 52 weeks after treatment initiation | 
| 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). It is designed to measure five domains of health related quality of life in breast cancer patients: physical, social, emotional, functional well-being as well as a breast-cancer sub-scale (BCS). | Baseline, 4, 8, 12 and 52 weeks after treatment initiation | 
| Endocrine therapy rates of non-compliance | Rates of non-persistence or non-compliance with initially prescribed endocrine therapy | 52 weeks after treatment initiation | 
| Cost-effectiveness | Incremental cost-effectiveness rations (cost per one quality-adjusted life year (QALY) gained). | 52 weeks after treatment initiation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast Cancer, Endocrine Therapy, Chronotherapy, Chronotherapeutics