RHEAL: Hypofractionated LocoRegional Radiotherapy in Breast Cancer

Sponsor
Ontario Clinical Oncology Group (OCOG) (Other)
Overall Status
Recruiting
CT.gov ID
NCT04228991
Collaborator
(none)
588
14
2
82.6
42
0.5

Study Details

Study Description

Brief Summary

The primary objective is to determine if hypofractionated radiotherapy (RT) delivered over 1 week to the breast and regional nodes (supraclavicular, axillary and internal mammary) following breast conserving surgery (BCS), or to the chest wall and regional nodes following mastectomy, is non-inferior to conventional fractionation delivered over 3 weeks in patients with node positive breast cancer.

Condition or Disease Intervention/Treatment Phase
  • Radiation: Locoregional radiation treatment - Conventional fractionation
  • Radiation: Locoregional radiation treatment - Hypofractionation
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
588 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Trial of Hypofractionated LocoRegional Radiotherapy in Breast Cancer and Lymphedema (RHEAL)
Actual Study Start Date :
Feb 10, 2021
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Dec 31, 2027

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Control

Conventional fractionation for locoregional radiotherapy

Radiation: Locoregional radiation treatment - Conventional fractionation
40 Gray in 15 daily fractions over 3 weeks

Experimental: Experimental

Hypofractionation for locoregional radiotherapy

Radiation: Locoregional radiation treatment - Hypofractionation
26 Gray in 5 daily fractions over 1 week

Outcome Measures

Primary Outcome Measures

  1. Lymphedema [3 years post randomization]

    Lymphedema defined as relative volume change (RVC) >10%

Secondary Outcome Measures

  1. Breast cancer recurrence [Annually for 5 years post randomization]

    Both locoregional and distant recurrence and second cancers

  2. Mortality [Annually for 5 years post randomization]

    Survival

  3. Radiation toxicity [During last week of radiotherapy, at 3 months post radiotherapy and annually for 5 years post randomization]

    Acute and late radiation toxicity

  4. Arm mobility [1 and 3 years post randomization]

    Assessed by measuring the straight lateral abduction of both the ipsilateral and contralateral arm

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
2 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
3 BC Cancer - Centre for the Southern Interior Kelowna British Columbia Canada V1Y 5L3
4 BC Cancer - Vancouver Island Centre Victoria British Columbia Canada V8R 6V5
5 Juravinski Cancer Centre Hamilton Ontario Canada L8V 5C2
6 London Regional Cancer Program London Ontario Canada N6A 5W9
7 Northeast Cancer Centre, Health Sciences North Sudbury Ontario Canada P3E5J1
8 Princess Margaret Cancer Centre - UHN Toronto Ontario Canada M5G 1E0
9 Hotel-Dieu de Lévis (CISSS CA) Lévis Quebec Canada G6V 3Z1
10 CIUSSS de l'Est-de-l'Île de Montréal, Hôpital, Maisonneuve-Rosemont Montreal Quebec Canada H1T 2M4
11 McGill University Health Centre-Cedars Cancer Centre Montréal Quebec Canada H4A 3J1
12 CHUM - Centre Hospitalier de L'Universite de Montreal Montréal Quebec Canada
13 CHU-de Québec-Université de Laval Quebec City Quebec Canada
14 Sherbrooke University Hospital Centre Sherbrooke Quebec Canada J1G 2E8

Sponsors and Collaborators

  • Ontario Clinical Oncology Group (OCOG)

Investigators

  • Principal Investigator: Timothy Whelan, Juravinski Cancer Centre, McMaster University, Hamilton

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Ontario Clinical Oncology Group (OCOG)
ClinicalTrials.gov Identifier:
NCT04228991
Other Study ID Numbers:
  • OCOG-2019-RHEAL
First Posted:
Jan 14, 2020
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ontario Clinical Oncology Group (OCOG)
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 23, 2022