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A Randomized Trial of Five Fraction Partial Breast Irradiation (RAPID2)

Phase 3
Recruiting
Conditions
Radiotherapy
Breast Neoplasm Female
Cosmetic Outcome
Interventions
Radiation: Whole Breast Irradiation (WBI)
Radiation: Partial Breast Irradiation (PBI)
Registration Number
NCT05417516
Lead Sponsor
Ontario Clinical Oncology Group (OCOG)
Brief Summary

The primary objective of this study is to determine in women with node negative BC ≤3cm in size, if PBI compared to WBI, both given once-a-day over 1 week following BCS, is non-inferior for LR and reduces adverse cosmesis. The primary outcomes are LR and patient-assessed cosmesis at 3 years post randomization.

Detailed Description

This is a randomized, two-arm, single blinded trial comparing two radiation treatment modalities, PBI and WBI. Following BCS or on the completion of additional adjuvant chemotherapy, eligible and consenting patients with newly diagnosed and histologically confirmed invasive carcinoma of the breast (without evidence of metastatic disease); with microscopically clear resection margins of 1mm (or no residual disease on re-excision) and negative axillary node involvement will be randomized in a 1:1 fashion to receive either PBI (experimental group) or WBI (control group). Study participants will receive 26Gy in 5 fractions in both treatment arms, treated once per day, for a period of 5-7 days. Study participants will not be made aware of treatment allocation to prevent any potential bias in their assessment of cosmesis. Stratification factors include tumour size, estrogen receptor (ER) status, and clinical centre.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
910
Inclusion Criteria

For inclusion in this study, patients must fulfill all of the following criteria:

  1. Female with a new histological diagnosis of invasive carcinoma of the breast with no evidence of metastatic disease (see AJCC TNM Cancer Staging, Appendix II).
  2. Treated by BCS with microscopically clear resection margins >= 1mm for invasive and non-invasive disease or no residual disease on re-excision.
  3. Negative axillary node involvement as determined by either sentinel lymph node biopsy or axillary node dissection or clinical assessment with a negative axillary ultrasound and/or biopsy, for women with unifocal tumours <= 2cm, histologic grade 1 or 2, ER or PR+ and HER2-ve that are being planned for endocrine therapy
Exclusion Criteria

Patients who satisfy any of the following exclusion criteria are NOT eligible for this study:

  1. Age less than 50 years.
  2. Known to be BRCA 1 and/or BRCA 2 positive.
  3. Tumour size >3cm in greatest diameter on pathological examination.
  4. Evidence of extensive intraductal component (EIC) (defined as an invasive tumour with a ductal carcinoma in situ (DCIS) component comprising at least 25% and extending beyond the invasive component to surrounding normal breast tissue) with the following exception: smaller tumours with EIC where the combined size (of the invasive and DCIS components) are <= 3cm remain eligible
  5. Evidence of a DCIS component > 3cm
  6. Lobular carcinoma only.
  7. More than one primary tumour in different quadrants of the same breast (patients with multifocal breast cancer are eligible).
  8. Synchronous or previous contralateral breast cancer (patients with contralateral DCIS or LCIS are eligible).
  9. History of non-breast malignancy within the last 5 years other than treated non-melanoma skin cancer or treated in-situ carcinoma.
  10. Known pregnancy or currently lactating.
  11. Inability to localize tumour bed on CT planning (no evidence of surgical clips or seroma).
  12. Inability to plan the patient for the experimental technique.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Whole Breast Irradiation (WBI)Whole Breast Irradiation (WBI)26 Gy in 5 fractions to the whole breast
Partial Breast Irradiation (PBI)Partial Breast Irradiation (PBI)26 Gy in 5 fractions to the tumour bed with a margin of normal tissue
Primary Outcome Measures
NameTimeMethod
Patient Assessment Cosmesis at 3 years3 and 5 years post-randomization

Cosmesis will be assessed by the patient using the Breast Cosmesis Questionnaire which incorporates the Modified EORTC Breast Cosmetic Rating System and the UK Patient Reported Outcomes Questions following BCS.

Local RecurrenceAnnually for 5 years post-randomization

Time from randomization to any evidence of tumour recurrence (invasive and non-invasive) in the treated breast.

Secondary Outcome Measures
NameTimeMethod
Distant Disease Free Survival (DDSF)Annually for 5 years post-randomization.

Time from randomization to evidence of metastasis involving distant sites (e.g. bone, liver, lung, or brain).

Overall Survival3 years post-randomizaton.

Time from randomization to death of any cause.

Patient Assessed Cosmesis at 5 years.5 years post-randomization.

Cosmesis will be assessed by the patient using the Breast Cosmesis Questionnaire which incorporates the Modified EORTC Breast Cosmetic Rating System13,27,42 and the UK Patient Reported Outcomes Questions following BCS.

Patient Reported Quality of Life2 weeks post-radiation treatment, then at 3 and 5 years post-randomization.

Patients will complete the EORTC Breast Cancer Quality of life questionnaire

Disease Free Survival (DFS)Annually for 5 years post-randomization.

Time from randomization to local recurrence, regional or distant recurrence, contralateral breast cancer, other second cancer, or death.

Radiation Toxicity2 weeks and 3 months post-radiation treatment, then annually for 5 years post-randomization.

Acute (2 weeks and up to 3 months after completing RT) and late toxicity (beyond the 3 months after completing RT) will be assessed by clinical centre personnel using the NCI CTCAE version 5.0.

Nurse/Clinical Research Associate assessed cosmesis at 3 and 5 years.3 and 5 years post-randomization.

A nurse/Clinical Research Associate (CRA) assessment of cosmesis using the EORTC Breast Cosmetic Rating System. Nurses and CRAs will be training in assessing cosmesis using training slides and guide previously developed for other trials.

Trial Locations

Locations (24)

GenesisCare Hurstville

🇦🇺

Hurstville, New South Wales, Australia

GenesisCare Mater Hospital

🇦🇺

North Sydney, New South Wales, Australia

GenesisCare Bundaberg

🇦🇺

Bundaberg, Queensland, Australia

GenesisCare Southport

🇦🇺

Southport, Queensland, Australia

GenesisCare Tugun

🇦🇺

Tugun, Queensland, Australia

GenesisCare St Andrew's

🇦🇺

Adelaide, South Australia, Australia

GenesisCare Fiona Stanley Hospital

🇦🇺

Murdoch, Western Austrailia, Australia

GenesisCare Hollywood

🇦🇺

Nedlands, Western Australia, Australia

Arthur J. E. Child Comprehensive Cancer Centre-Clinical Research Unit

🇨🇦

Calgary, Alberta, Canada

BCCA-Vancouver Island Cancer Centre

🇨🇦

Victoria, British Columbia, Canada

QEII HSC - Nova Scotia Cancer Centre

🇨🇦

Halifax, Nova Scotia, Canada

Royal Victoria Regional Health Centre

🇨🇦

Barrie, Ontario, Canada

Juravinski Cancer Centre

🇨🇦

Hamilton, Ontario, Canada

London Regional Cancer Centre

🇨🇦

London, Ontario, Canada

Stronach (Southlake) Regional Health Centre

🇨🇦

Newmarket, Ontario, Canada

Algoma District Cancer Program

🇨🇦

Sault-Sainte-Marie, Ontario, Canada

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Toronto-Sunnybrook Health Sciences Centre - Odette Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

🇨🇦

Windsor, Ontario, Canada

CSSS Champlain - Charles LeMoyne

🇨🇦

Greenfield Park, Quebec, Canada

McGill University Health Centre

🇨🇦

Montréal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

🇨🇦

Québec, Quebec, Canada

Centre Intégré Universitaire de Santé et de Services Sociaux de la Mauricie-Centre-du-Québec (CIUSSS MCQ)

🇨🇦

Trois-Rivières, Quebec, Canada

Saskatoon Cancer Centre

🇨🇦

Saskatoon, Saskatchewan, Canada

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