Hypofractionated LocoRegional Radiotherapy in Breast Cancer

Phase 3

Recruiting

• Conditions: Breast Neoplasms; Radiotherapy; Lymphedema
• Interventions: Radiation: Locoregional radiation treatment - Conventional fractionation; Radiation: Locoregional radiation treatment - Hypofractionation

• Registration Number: NCT04228991
• Lead Sponsor: Ontario Clinical Oncology Group (OCOG)

Brief 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.

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.

Study Timeline

• Study First Submitted: 2020-01-09
• Study First Submitted QC: 2020-01-10
• Study First Posted: 2020-01-14
• Study Start: 2021-02-10
• Status Verified: 2024-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-09
• Primary Completion: 2025-09-30
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 588

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Locoregional radiation treatment - Conventional fractionation	Conventional fractionation for locoregional radiotherapy
Experimental	Locoregional radiation treatment - Hypofractionation	Hypofractionation for locoregional radiotherapy

Primary Outcome Measures

Name	Time	Method
Lymphedema	3 years post randomization	Lymphedema defined as relative volume change (RVC) ≥10%

Secondary Outcome Measures

Name	Time	Method
Breast cancer recurrence	Annually for 5 years post randomization	Both locoregional and distant recurrence and second cancers
Patient Quality of Life with respect to daily health and activities	During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization	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.
Perception of lymphedema	During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization	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.
Arm mobility	1 and 3 years post randomization	Assessed by measuring the straight lateral abduction of both the ipsilateral and contralateral arm
Perception of breast cosmesis	1 and 3 years post randomization	Patient-reported breast cosmesis using a Breast Cosmesis Questionnaire to study the late effects of radiation.
Mortality	Annually for 5 years post randomization	Survival
Radiation toxicity	During last week of radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization	Acute and late radiation toxicity
Health Care Resource Utilization	During radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization	Health Care Resource Utilization will be estimated using dates and duration of radiotherapy treatment and emergency department visits and hospitalizations.
Patient Costs	During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization	Patient costs will be assessed using a Time Off Work Questionnaire to study the financial impact of breast cancer and its treatment

Trial Locations

Locations (20)

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

BC Cancer - Centre for the Southern Interior; 🇨🇦 Kelowna, British Columbia, Canada

BC Cancer - Centre for the North; 🇨🇦 Prince George, British Columbia, Canada

BC Cancer - Vancouver Centre; 🇨🇦 Vancouver, British Columbia, Canada

BC Cancer - Vancouver Island Centre; 🇨🇦 Victoria, British Columbia, Canada

Juravinski Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada

The Ottawa Hospital Regional Cancer Centre; 🇨🇦 Ottawa, Ontario, Canada

Northeast Cancer Centre, Health Sciences North; 🇨🇦 Sudbury, Ontario, Canada

Sunnybrook Health Sciences Centre - Odette Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Princess Margaret Cancer Centre - UHN; 🇨🇦 Toronto, Ontario, Canada

Hotel-Dieu de Lévis (CISSS CA); 🇨🇦 Lévis, Quebec, Canada

CIUSSS de l'Est-de-l'Île de Montréal, Hôpital, Maisonneuve-Rosemont; 🇨🇦 Montreal, Quebec, Canada

McGill University Health Centre-Cedars Cancer Centre; 🇨🇦 Montréal, Quebec, Canada

CHUM - Centre Hospitalier de L'Universite de Montreal; 🇨🇦 Montréal, Quebec, Canada

CHU-de Québec-Université de Laval; 🇨🇦 Quebec City, Quebec, Canada

Sherbrooke University Hospital Centre; 🇨🇦 Sherbrooke, Quebec, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada