Evaluating Optimal Timing of Endocrine Therapy and Radiation Therapy in Early-stage Breast Cancer (REaCT-RETT) (REaCT-RETT)

A Pragmatic Randomised, Multicentre Trial Evaluating Optimal Timing of Endocrine Therapy and Radiation Therapy in Early-stage Breast Cancer (REaCT-RETT)

REaCT-RETT will demonstrate the non-inferiority of concurrent compared to sequential endocrine therapy in patients receiving post-operative radiotherapy for early stage breast cancer.

Study Overview

• Status: Completed
• Conditions: Early-stage Breast Cancer
• Intervention / Treatment: Combination product: Endocrine Therapy and Radiotherapy

Detailed Description

Clinical equipoise exists around the optimal time to start adjuvant endocrine therapy in patients who will receive post-operative radiotherapy for breast cancer. Patients receive either concurrent or sequential endocrine and radiation therapy, where concurrent therapy consists of endocrine therapy started before, with or during radiotherapy, while sequential treatment is defined as endocrine therapy starting after the completion of radiotherapy. A recent survey of Canadian oncologists showed that the main reason for prescribing sequential endocrine therapy was a concern that concurrent endocrine therapy and radiotherapy would worsen the toxicity of endocrine treatment. This is despite the absence of any clinical trial evidence to support this. Indeed, a recent systematic review by our group was unable to confirm or refute whether increased toxicities, related to the timing of endocrine therapy and radiotherapy actually exist in clinical practice. The investigators are therefore proposing a pragmatic randomised trial to assess whether or not concurrent endocrine therapy and radiotherapy worsens endocrine treatment-related symptoms in an era of modern endocrine and radiation therapy.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8M2
      • Ottawa Hospital Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with newly diagnosed early stage, hormone receptor positive breast cancer
• Planned to receive both endocrine therapy and post-operative radiotherapy
• Able to provide verbal consent

Exclusion Criteria:

• Previous endocrine therapy for invasive breast cancer
• Previous radiotherapy for breast cancer in the same breast

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Concurrent Endocrine Therapy and Radiotherapy; Concurrent endocrine therapy and radiotherapy. Concurrent endocrine therapy will be defined as, the commencement of endocrine therapy around 2 weeks before (a minimum of 1 week before to a maximum of 4 weeks) commencement of radiotherapy and continued throughout radiotherapy.	Combination product: Endocrine Therapy and Radiotherapy; Endocrine therapy and radiotherapy administered either concurrently or sequentially; Other Names: Radiotherapy; Exemestane; Letrozole; Anastrozole; Tamoxifen
ACTIVE_COMPARATOR: Sequential Endocrine Therapy after Radiotherapy; Sequential endocrine therapy after radiotherapy. Using the pragmatic definition sequential endocrine therapy should commence around 2 weeks (minimum 1 week, maximum 4 weeks) after the last fraction of radiotherapy.	Combination product: Endocrine Therapy and Radiotherapy; Endocrine therapy and radiotherapy administered either concurrently or sequentially; Other Names: Radiotherapy; Exemestane; Letrozole; Anastrozole; Tamoxifen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endocrine toxicity	To measure endocrine toxicity. The Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) is a questionnaire specific to patients with endocrine symptoms and measures the side effects and putative benefits of hormonal treatments given (endocrine therapy) in breast cancer. The FACT-ES questionnaire is comprised of 5 sections; physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), functional well-being (7 questions) and additional concerns (19 questions). A total of 46 questions are asked that all contain an answer on a scale range of 0-4, with 0 representing the answer 'not at all' and 4 representing the answer 'very much'. Of the 46 questions asked 31/46 have 'very much' representing the worst answer and the remaining 15/46 have 'very much' representing the best answer.	12 months (+/- 2 weeks) post final fraction of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiotherapy toxicity	To evaluate the acute and early-moderate late toxicities of radiotherapy in terms of skin toxicity, pneumonitis, and breast pain. This will be recorded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with breast cosmesis recorded as per the European Organisation for Research and Treatment of Cancer (EORTC) cosmetic rating system for breast cancer. These standardized criteria have been used in a recent Canadian breast radiation randomized trial, RAPID, and the investigators will use a similar template to record any radiation toxicities at different points of time.	12 months (+/- 2 weeks) post final fraction of radiotherapy
Rates of starting endocrine therapy and compliance	Rates of starting endocrine therapy, compliance rates, discontinuation rates, along with the reasons for discontinuation.	12 months (+/- 2 weeks) post final fraction of radiotherapy
Direct Estimation of Health Utility Values	To measure the patient quality of life using the validated FACT-B questionnaire. The Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) is a questionnaire that measures multidimensional quality of life in patients with breast cancer. The FACT-B questionnaire is comprised of 5 sections; physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), functional well-being (7 questions) and additional concerns (10 questions). A total of 37 questions are asked that all contain an answer on a scale range of 0-4, with 0 representing the answer 'not at all' and 4 representing the answer 'very much'. Of the 46 questions asked 20/37 have 'very much' representing the worst answer and the remaining 17/37 have 'very much' representing the best answer.	12 months (+/- 2 weeks) post final fraction of radiotherapy
Incremental cost-effectiveness ratios	Incremental cost-effectiveness ratios (cost per one quality-adjusted life year (QALY) gained and cost per one endocrine toxicity case averted) will be measured using the EQ-5D-5L questionnaire. The EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaire consists of two sections; the descriptive system and the visual analogue scale. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and has 5 levels associated with it (no problems, slight problems, moderate problems, severe problems and extreme problems). The scale range of 1-5 is used for the 5 dimensions where 1 is the best outcome and 5 is the worst outcome. The Visual Analogue scale records the respondent's self-rated health on a vertical, visual scale with endpoints labelled "the best health you can imagine" at the top and "the worst health you can imagine" at the bottom. This ranges 0-100 with 0 being the worst outcome and 100 being the best outcome.	12 months (+/- 2 weeks) post final fraction of radiotherapy
Exploratory analyses on evaluating radiotherapy toxicity	Exploratory analyses will be performed evaluating toxicity in patients receiving different types of radiotherapy (i.e. local versus regional radiotherapy). This will be evaluated using data collected on breast volume, seroma size, dose heterogeneity and the time of stimulation and planning.	12 months (+/- 2 weeks) post final fraction of radiotherapy

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Jean Marc Bourque, MD, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2019
• Primary Completion (ACTUAL): June 9, 2021
• Study Completion (ACTUAL): April 9, 2022

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (ACTUAL): May 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Radiation Therapy; Endocrine Therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Anastrozole; Exemestane
• Other Study ID Numbers: OTT 18-02

Drug and device information, study documents

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