Hypofractionated LocoRegional Radiotherapy in Breast Cancer (RHEAL)

Ontario Clinical Oncology Group (OCOG)

Status and phase: Enrolling; Phase 3

Conditions: Lymphedema; Radiotherapy; Breast Neoplasms

Treatments: Radiation: Locoregional radiation treatment - Hypofractionation; Radiation: Locoregional radiation treatment - Conventional fractionation

Study type: Interventional

Funder types: Other

Identifiers

NCT04228991

OCOG-2019-RHEAL

Details and patient eligibility

About

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.

Full 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.

Enrollment: 588 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

588 participants in 2 patient groups

Control

Active Comparator group

Description:

Conventional fractionation for locoregional radiotherapy

Treatment:

Radiation: Locoregional radiation treatment - Conventional fractionation

Experimental

Experimental group

Description:

Hypofractionation for locoregional radiotherapy

Treatment:

Radiation: Locoregional radiation treatment - Hypofractionation