Breast Cancer, Cancer

Phase 3

Interventional Study

Hypofractionated LocoRegional Radiotherapy in Breast Cancer (RHEAL)

Sponsor

Ontario Clinical Oncology Group (OCOG)

Start Date

10/02/2021

Completion Date

30/09/2023

Sex

ALL

Enrollment

588

Ages From

18

Healthy Volunteers?

Yes

Contact

Brittany Speller

Location

Tom Baker Cancer Centre

Trial Details

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.

Official Title

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

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.

Selection Criteria

Eligibility Inclusion Criteria

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.

Eligibility Exclusion Criteria

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.
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.

ARMS & Interventions

PARTICIPANT GROUP ARMINTERVENTION TREATMENT
Active Comparator: Control Conventional fractionation for locoregional radiotherapyRadiation: Locoregional radiation treatment - Conventional fractionation 40 Gray in 15 daily fractions over 3 weeks
Experimental: Experimental Hypofractionation for locoregional radiotherapyRadiation: Locoregional radiation treatment - Hypofractionation 26 Gray in 5 daily fractions over 1 week

Primary Outcome

MeasuresMeasure DescriptionMEASURE TIME FRAME
LymphedemaLymphedema defined as relative volume change (RVC) >10%3 years post randomization

Secondary Outcome

MEASURESMEASURE DESCRIPTIONMEASURE TIME FRAME
Breast cancer recurrenceBoth locoregional and distant recurrence and second cancers Annually for 5 years post randomization
MortalitySurvivalAnnually for 5 years post randomization
Radiation toxicityAcute and late radiation toxicityDuring last week of radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization
Arm mobilityAssessed by measuring the straight lateral abduction of both the ipsilateral and contralateral arm1 and 3 years post randomization
During last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomizationDuring last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomizationDuring last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization
Perception of lymphedemaImpact 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.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.
Perception of breast cosmesisPatient-reported breast cosmesis using a Breast Cosmesis Questionnaire to study the late effects of radiation.1 and 3 years post randomization
Health Care Resource UtilizationHealth 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
Patient CostsPatient costs will be assessed using a Time Off Work Questionnaire to study the financial impact of breast cancer and its treatmentDuring last week of radiotherapy, at 3 months post radiotherapy and 1 and 3 years post randomization

Other Outcome

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