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

Official title

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

Overview

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.

Interventions

• Radiation Whole Breast Irradiation (WBI)
  The dose fractionation and prescription is 26Gy in 5 fractions to the PTV once per day over 5-7 days (due to holiday weekends up to 8 days will be acceptable).
• Radiation Partial Breast Irradiation (PBI)
  The dose fractionation and prescription is 26Gy in 5 fractions to the PTV prescribed at the isocentre of the treatment fields treated once per day over 5-7 days (due to holiday weekends up to 8 days will be acceptable).

Primary outcome measures

• Local Recurrence [Time frame: Annually for 5 years post-randomization]
• Patient Assessment Cosmesis at 3 years [Time frame: 3 and 5 years post-randomization]

Secondary outcome measures (7)

• Distant Disease Free Survival (DDSF) [Time frame: Annually for 5 years post-randomization.]
• Disease Free Survival (DFS) [Time frame: Annually for 5 years post-randomization.]
• Overall Survival [Time frame: 3 years post-randomizaton.]
• Radiation Toxicity [Time frame: 2 weeks and 3 months post-radiation treatment, then annually for 5 years post-randomization.]
• Nurse/Clinical Research Associate assessed cosmesis at 3 and 5 years. [Time frame: 3 and 5 years post-randomization.]
• Patient Assessed Cosmesis at 5 years. [Time frame: 5 years post-randomization.]
• Patient Reported Quality of Life [Time frame: 2 weeks post-radiation treatment, then at 3 and 5 years post-randomization.]

Eligibility criteria

Inclusion criteria

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

• 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).
• Treated by BCS with microscopically clear resection margins >= 1mm for invasive and non-invasive disease or no residual disease on re-excision.
• 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:

• Age less than 50 years.
• Known to be BRCA 1 and/or BRCA 2 positive.
• Tumour size >3cm in greatest diameter on pathological examination.
• 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
• Evidence of a DCIS component > 3cm
• Lobular carcinoma only.
• More than one primary tumour in different quadrants of the same breast (patients with multifocal breast cancer are eligible).
• Synchronous or previous contralateral breast cancer (patients with contralateral DCIS or LCIS are eligible).
• History of non-breast malignancy within the last 5 years other than treated non-melanoma skin cancer or treated in-situ carcinoma.
• Known pregnancy or currently lactating.
• Inability to localize tumour bed on CT planning (no evidence of surgical clips or seroma).
• Inability to plan the patient for the experimental technique.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 18 centers

• Arthur J. E. Child Comprehensive Cancer Centre-Clinical Research Unit — Calgary
• BCCA-Vancouver Island Cancer Centre — Victoria
• QEII HSC - Nova Scotia Cancer Centre — Halifax
• Royal Victoria Regional Health Centre — Barrie
• Juravinski Cancer Centre — Hamilton
• London Regional Cancer Centre — London
• Stronach (Southlake) Regional Health Centre — Newmarket
• Algoma District Cancer Program — Sault Ste. Marie
• … and 10 more centers

Australia · 12 centers

• GenesisCare Darlinghurst — Darlinghurst
• GenesisCare Hurstville — Hurstville
• GenesisCare Mater Hospital — North Sydney
• GenesisCare Bundaberg — Bundaberg
• GenesisCare Southport — Southport
• GenesisCare Tugun — Tugun
• GenesisCare Hervey Bay — Urraween
• GenesisCare St Andrew's — Adelaide
• … and 4 more centers

Identifiers

NCT: NCT05417516 · OCOG-2022-RAPID2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗