Clinical trial NCT04228991: Hypofractionated LocoRegional Radiotherapy in Breast Cancer
Official title: Randomized Trial of Hypofractionated LocoRegional Radiotherapy in Breast Cancer and Lymphedema (RHEAL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Neoplasms
Radiotherapy
Lymphedema
Keywords: Hypofractionated
Locoregional
Breast Cancer
Lymphedema
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
First posted: 2020-01-14
Enrollment: 588
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Lymphedema
timeFrame: 3 years post randomization
Secondary outcomes:
measure: Breast cancer recurrence
timeFrame: Annually for 5 years post randomization
measure: Mortality
timeFrame: Annually for 5 years post randomization
measure: Radiation toxicity
timeFrame: During last week of radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
measure: Arm mobility
timeFrame: 1 and 3 years post randomization
measure: Patient Quality of Life with respect to daily health and activities
timeFrame: During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
measure: Perception of lymphedema
timeFrame: During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
measure: Perception of breast cosmesis
timeFrame: 1 and 3 years post randomization
measure: Health Care Resource Utilization
timeFrame: During radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
measure: Patient Costs
timeFrame: During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BC Cancer - Centre for the Southern Interior
state: British Columbia
city: Prince George
country: Canada
facility: BC Cancer - Centre for the North
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer - Vancouver Centre
state: British Columbia
city: Victoria
country: Canada
facility: BC Cancer - Vancouver Island Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Centre, Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre - Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - UHN
state: Ontario
city: Lévis
country: Canada
facility: Hotel-Dieu de Lévis (CISSS CA)
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-l'Île de Montréal, Hôpital, Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre-Cedars Cancer Centre
state: Quebec
city: Montréal
country: Canada
facility: CHUM - Centre Hospitalier de L'Universite de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: CHU-de Québec-Université de Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Sherbrooke University Hospital Centre
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Juravinski Cancer Centre, McMaster University, Hamilton
name: Timothy Whelan, MD
role: PRINCIPAL_INVESTIGATOR
References: