Hypofractionated LocoRegional Radiotherapy in Breast Cancer

Breast Neoplasms Clinical Trial

— RHEAL  

Official title:

Randomized Trial of Hypofractionated LocoRegional Radiotherapy in Breast Cancer and Lymphedema (RHEAL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04228991
• Other study ID #: OCOG-2019-RHEAL
• Status: Recruiting
• Phase: Phase 3
• Start date: February 10, 2021
• Est. completion date: December 31, 2030

Study information

• Verified date: May 2024
• Source: Ontario Clinical Oncology Group (OCOG)
• Contact: Brittany Speller
• Phone: 905-527-2299
• Email: spelleb[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 (40Gy in 15 daily fractions) in patients with node-positive breast cancer.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 588
• Est. completion date: December 31, 2030
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Newly diagnosed invasive carcinoma of the breast.

2. 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.

3. 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.

4. No evidence of metastatic disease.

Exclusion Criteria:

1. Age < 18 years.

2. Clinical stages T4 and/or N3.

3. Clinical lymphedema in the ipsilateral arm or breast/chest wall.

4. 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.)

5. Synchronous or previous contralateral breast cancer.(Patients with previous contralateral DCIS or LCIS not treated with radiation are eligible.)

6. History of non-breast malignancy within the last 5 years other than non-melanoma skin cancer or treated in-situ carcinoma.

7. Neoadjuvant endocrine therapy. (Extended neoadjuvant endocrine therapy is not permitted. Endocrine therapy exposure for 12 weeks or less prior to surgery is acceptable.)

8. Breast reconstruction.

9. Presence of known medical conditions that would preclude follow-up for 5 years.

10. 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.

11. Known pregnancy or currently lactating.

12. Geographic inaccessibility for follow-up.

13. Inability to provide informed consent.

Related Conditions & MeSH terms

• Breast Neoplasms
• Lymphedema
• Radiotherapy

Intervention

Radiation:
• Locoregional radiation treatment - Conventional fractionation
40 Gray in 15 daily fractions over 3 weeks
• Locoregional radiation treatment - Hypofractionation
26 Gray in 5 daily fractions over 1 week

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	BC Cancer - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Hotel-Dieu de Lévis (CISSS CA)	Lévis	Quebec
Canada	London Regional Cancer Program	London	Ontario
Canada	CIUSSS de l'Est-de-l'Île de Montréal, Hôpital, Maisonneuve-Rosemont	Montreal	Quebec
Canada	CHUM - Centre Hospitalier de L'Universite de Montreal	Montréal	Quebec
Canada	McGill University Health Centre-Cedars Cancer Centre	Montréal	Quebec
Canada	The Ottawa Hospital Regional Cancer Centre	Ottawa	Ontario
Canada	CHU-de Québec-Université de Laval	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Sherbrooke University Hospital Centre	Sherbrooke	Quebec
Canada	Northeast Cancer Centre, Health Sciences North	Sudbury	Ontario
Canada	Princess Margaret Cancer Centre - UHN	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre - Odette Cancer Centre	Toronto	Ontario
Canada	BC Cancer - Vancouver Centre	Vancouver	British Columbia
Canada	BC Cancer - Vancouver Island Centre	Victoria	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ontario Clinical Oncology Group (OCOG)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lymphedema	Lymphedema defined as relative volume change (RVC) =10%	3 years post randomization
Secondary	Breast cancer recurrence	Both locoregional and distant recurrence and second cancers	Annually for 5 years post randomization
Secondary	Mortality	Survival	Annually for 5 years post randomization
Secondary	Radiation toxicity	Acute and late radiation toxicity	During last week of radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
Secondary	Arm mobility	Assessed by measuring the straight lateral abduction of both the ipsilateral and contralateral arm	1 and 3 years post randomization
Secondary	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.	During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Secondary	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.	During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Secondary	Perception of breast cosmesis	Patient-reported breast cosmesis using a Breast Cosmesis Questionnaire to study the late effects of radiation.	1 and 3 years post randomization
Secondary	Health Care Resource Utilization	Health Care Resource Utilization will be estimated using dates and duration of radiotherapy treatment and emergency department visits and hospitalizations.	During radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
Secondary	Patient Costs	Patient costs will be assessed using a Time Off Work Questionnaire to study the financial impact of breast cancer and its treatment	During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization