Breast NeoplasmsPhase 3RHEALNCT04228991
Hypofractionated LocoRegional Radiotherapy in Breast Cancer
A Phase 3 study testing Locoregional radiation treatment - Conventional fractionation and Locoregional radiation treatment - Hypofractionation in people with Breast Neoplasms and Radiotherapy, run by Ontario Clinical Oncology Group (OCOG) at 20 sites in Canada.
Trial summary
The primary objective of this study is to determine if hypofractionated RT delivered over 1 week to the breast or chest wall and regional nodes (26Gy in 5 daily fractions) following BCS or mastectomy, is non-inferior to conventional fractionation to the breast or chest wall and regional nodes delivered over 3 weeks… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms, Radiotherapy, Lymphedema
- What is being tested?
- Locoregional radiation treatment - Conventional fractionation and Locoregional radiation treatment - Hypofractionation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 588 participants
- Where
- 20 sitesCanada
- Study dates
- 10 Feb 2021to 31 Dec 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed invasive carcinoma of the breast.
- Treated with definitive surgery (BCS or mastectomy with nodal staging using SLNB or ALND) with clear margins of excision.* Note: *Patients with limited positive posterior margin where disease is resected to chest wall or limited positive anterior margin where disease is resected to dermis are eligible.
- Candidate for locoregional radiotherapy: breast cancer stage after definitive surgery:
- Neoadjuvant chemotherapy was not administered: pathologic stage T3N0,T1-3 N1-2**
- patients with nodal micromets (N1mi) are eligible
- Neoadjuvant chemotherapy was administered: clinical stage T3N0, T1-3, N1-2 and pathologic stage T0-3, N0-2†
- Patients who are clinically N1-2 prior to chemotherapy should be confirmed histologically unless it is clear that they are node positive. Patients who are deemed node negative prior to chemotherapy but are node positive following chemotherapy are eligible. Patients who are node positive prior to chemotherapy and who have complete response in the lymph nodes are also eligible.
- No evidence of metastatic disease.
Who cannot join
- Age < 18 years.
- Clinical stages T4 and/or N3.
- Clinical lymphedema in the ipsilateral arm or breast/chest wall.
- Any prior history, not including index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy. (Patients with previous ipsilateral DCIS or LCIS not treated with radiation are eligible.)
- Synchronous or previous contralateral breast cancer.(Patients with previous contralateral DCIS or LCIS not treated with radiation are eligible.)
- History of non-breast malignancy within the last 5 years other than non-melanoma skin cancer or treated in-situ carcinoma.
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- Neoadjuvant endocrine therapy. (Extended neoadjuvant endocrine therapy is not permitted. Endocrine therapy exposure for 12 weeks or less prior to surgery is acceptable.)
- Breast reconstruction.
- Presence of known medical conditions that would preclude follow-up for 5 years.
- Previous radiotherapy to the ipsilateral breast or chest wall or serious non-malignant disease e.g. scleroderma, severe lung or heart disease that would preclude radiotherapy.
- Known pregnancy or currently lactating.
- Geographic inaccessibility for follow-up.
- Inability to provide informed consent.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Canada20 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Northeast Cancer Centre, Health Sciences North
Greater Sudbury, Ontario, P3E5J1
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2
BC Cancer - Centre for the Southern Interior
Kelowna, British Columbia, V1Y 5L3
Hotel-Dieu de Lévis (CISSS CA)
Lévis, Quebec, G6V 3Z1
London Regional Cancer Program
London, Ontario, N6A 5W9
CIUSSS de l'Est-de-l'Île de Montréal, Hôpital, Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
McGill University Health Centre-Cedars Cancer Centre
Montreal, Quebec, H4A 3J1
CHUM - Centre Hospitalier de L'Universite de Montreal
Montreal, Quebec
The Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, K1H 8L6
BC Cancer - Centre for the North
Prince George, British Columbia
CHU-de Québec-Université de Laval
Québec, Quebec
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Sherbrooke University Hospital Centre
Sherbrooke, Quebec, J1G 2E8
Sunnybrook Health Sciences Centre - Odette Cancer Centre
Toronto, Ontario, M4N 3M5
Princess Margaret Cancer Centre - UHN
Toronto, Ontario, M5G 1E0
BC Cancer - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
BC Cancer - Vancouver Island Centre
Victoria, British Columbia, V8R 6V5
About this study
Official title: Randomized Trial of Hypofractionated LocoRegional Radiotherapy in Breast Cancer and Lymphedema (RHEAL)
The primary objective of this study is to determine if hypofractionated RT delivered over 1 week to the breast or chest wall and regional nodes (26Gy in 5 daily fractions) following BCS or mastectomy, is non-inferior to conventional fractionation to the breast or chest wall and regional nodes delivered over 3 weeks (40Gy in 15 daily fractions) in patients with node-positive breast cancer.
Read the detailed description
A multi-centre, randomized, non-inferior, phase III study comparing two radiation treatment modalities, conventional fractionation with hypofractionation for locoregional RT. Eligible, consenting patients with newly diagnosed and histologically confirmed invasive carcinoma of the breast without evidence of metastatic disease; treated with definitive surgery [BCS or mastectomy with nodal staging using sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND)] will be randomized in a 1:1 fashion to either conventional locoregional RT (control group) or hypofractionated locoregional RT (experimental group). Stratification factors include: body mass index, the performance of ALND, type of surgery (BCS or mastectomy) and clinical centre.
Study participants will be assessed for lymphedema, the primary outcome, by measuring arm volume. Arm mobility will be assessed by measuring arm movement. Study participants will be assessed for acute and late radiation toxicities, during and post RT. Study participants will be followed and assessed annually for breast cancer recurrence (BCR), new second cancers, quality of life (QOL) and overall survival. Cost effectiveness and cost utility will also be determined. The planned sample size is 588 study participants. The study will be conducted at clinical centres throughout Canada.
- Conditions
- Breast Neoplasms, Radiotherapy, Lymphedema
- Being tested
- Locoregional radiation treatment - Conventional fractionation, Locoregional radiation treatment - Hypofractionation
- Keywords
- Hypofractionated, Locoregional, Breast Cancer, Lymphedema
- Medical subject headings
- Breast Neoplasms, Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Locoregional radiation treatment - Conventional fractionationRadiation
40 Gray in 15 daily fractions over 3 weeks
Locoregional radiation treatment - HypofractionationRadiation
26 Gray in 5 daily fractions over 1 week
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Conventional fractionation for locoregional radiotherapy Receives: Radiation: Locoregional radiation treatment - Conventional fractionation |
| Experimental | Experimental | Hypofractionation for locoregional radiotherapy Receives: Radiation: Locoregional radiation treatment - Hypofractionation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lymphedema
Lymphedema defined as relative volume change (RVC) ≥10%
Measured: 3 years post randomization
Secondary outcomes (9)
Breast cancer recurrence
Both locoregional and distant recurrence and second cancers
Measured: Annually for 5 years post randomization
Mortality
Survival
Measured: Annually for 5 years post randomization
Radiation toxicity
Acute and late radiation toxicity
Measured: During last week of radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
Arm mobility
Assessed by measuring the straight lateral abduction of both the ipsilateral and contralateral arm
Measured: 1 and 3 years post randomization
Patient Quality of Life with respect to daily health and activities
Impact on quality of life will be assessed with the European Organization for Research in Treatment of Cancer and the Breast Cancer Specific Module 23. The scale is 1 to 4 where a higher score means a worse outcome.
Measured: During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Perception of lymphedema
Impact of lymphedema on quality of life will be assessed with the National Surgical Adjuvant Breast and Bowel Project questionnaire. The scale is 1 to 5 where a higher score means a worse outcome.
Measured: During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Perception of breast cosmesis
Patient-reported breast cosmesis using a Breast Cosmesis Questionnaire to study the late effects of radiation.
Measured: 1 and 3 years post randomization
Health Care Resource Utilization
Health Care Resource Utilization will be estimated using dates and duration of radiotherapy treatment and emergency department visits and hospitalizations.
Measured: During radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
Patient Costs
Patient costs will be assessed using a Time Off Work Questionnaire to study the financial impact of breast cancer and its treatment
Measured: During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start10 Feb 2021
- Primary completionJul 2028 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 588 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ontario Clinical Oncology Group (OCOG)
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), McMaster University
- Responsible party
- Sponsor
- Investigators
- Timothy Whelan, MD, Principal investigator, Juravinski Cancer Centre, McMaster University, Hamilton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04228991
- Sponsor's protocol ID
- OCOG-2019-RHEAL
- Acronym
- RHEAL
- Status last verified
- Oct 2026
- First submitted
- 9 Jan 2020
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No