SIGNAL During a COVID-19 Pandemic

Single Fraction Preoperative Radiation as a Strategy for Local Control of Breast Cancer During a COVID-19 Pandemic

The standard treatment for early stage, estrogen-receptor positive breast cancer is lumpectomy and sentinel lymph node biopsy followed by 16-25 treatments of adjuvant whole-breast radiation therapy plus or minus hormone therapy. However, the COVID-19 pandemic has necessitated changes in the way breast cancer is treated in order to reduce contact between individuals, reduce spread of the novel coronavirus, and lessen the impact on health care resources. As elective surgeries are being cancelled, current pandemic guidelines recommend that patients be started on hormone treatment while waiting for surgeries to be re-instated. Only after this surgery occurs will patients receive radiation treatment, dramatically extending the time between diagnosis and end of treatment. Emergency pandemic guidelines in the UK and other countries recommend 5 fractions of pre-operative radiation therapy where appropriate. Based on previous work in the SIGNAL 1.0 and SIGNAL 2.0 clinical trials, the investigators are proposing treating patients with early stage breast cancers with one single fraction of stereotactic neoadjuvant radiation during the pre-operative waiting period. This will allow patients to complete radiation therapy upfront while reducing the number of patient visits to hospital. This will also allow investigators to evaluate the ability of single-fraction targeted radiation to induce a pathologic complete response.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Radiation therapy

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female sex
• Age ≥ 50 years old
• Postmenopausal
• Tumor size < 3cm on pre-treatment imaging
• Any grade of disease, estrogen receptor (ER) positive, HER2 negative
• Unicentric/unifocal disease
• Invasive ductal carcinoma or other favorable subtypes of epithelial breast malignancy (lobular, medullary, papillary, colloid, mucinous, or tubular) .
• Clinically node-negative (based upon pre-treatment physical examination and/or axillary ultrasound).
• Surgical expectation that a > 2mm margin can be obtained.
• Lesion is 1 cm or greater from the skin surface.
• Able to lie comfortably in the prone position with arms raised above the head for extended periods of time.

Exclusion Criteria:

• Male sex
• Under 50 years of age
• Previous RT to the same breast
• HER2 positive disease
• Evidence of suspicious diffuse microcalcifications in the breast prior to the start of radiation.
• Local metastatic spread into ipsilateral axilla and/or supraclavicular region and/or neck nodes and/or internal mammary nodes diagnosed on clinical examination or any imaging assessment (unless such sites can be confirmed as negative following biopsy)
• Distant metastases
• Involvement of contralateral axillary, supraclavicular, infraclavicular or internal mammary nodes (unless there is histologic confirmation that these nodes are negative)
• Prior non-hormonal therapy or radiation therapy for the current breast cancer
• Patients with Paget's disease of the nipple.
• Skin involvement, regardless of tumor size.
• Patients with a breast technically unsatisfactory for radiation therapy.
• Inability to lie prone with arms raised above head for extended periods of time.
• Patients not appropriate for BCS due to expectation of poor cosmetic result, even without RT
• Collagen vascular disease (particularly lupus, scleroderma, dermatomyositis)
• Inability or unwillingness to provide informed consent.
• Any other malignancy at any site (except non-melanomatous skin cancer) < 5 years prior to study enrollment
• Patients who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single fraction radiotherapy; Single fraction of 21 Gy stereotactic radiation therapy delivered to a single malignant lesion of the breast prior to any other treatment for breast cancer.	Procedure: Radiation therapy; Women diagnosed with early stage breast cancer are given a single dose of stereotactic body radiation therapy (SBRT) prior to any other treatment in the context of delayed lumpectomy due to the COVID-19 pandemic.; Other Names: Radiotherapy; Stereotactic body radiation therapy (SBRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response (pCR)	To evaluate whether a pathologic complete response can be achieved when radiotherapy is delivered in a single 21 Gy fraction, establishing whether tumour response has a linear function with time in the context of delayed surgery. Pathologic complete response will be treated as a dichotomous variable (yes/no). Results will be stratified based on whether patients were also placed on neoadjuvant hormone treatment.	1 year
Feasibility of SBRT during a pandemic	To demonstrate feasibility of treating early stage breast cancer patients with a single 21 Gy fraction during the COVID-19 pandemic. This will be measured by accrual rate and the number of patients that can be treated during this pandemic.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation toxicity	A secondary objective is to evaluate toxicity resulting from delivering radiation therapy in this manner. Toxicity will be evaluated using the CTCAE grading system.	1.5 years
Cosmesis	A secondary objective is to evaluate breast cosmesis resulting from delivery of radiation therapy in this manner. Cosmesis will be evaluated using the Modified Harvard-Harris Scale.	1.5 years

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Muriel Brackstone, MD, PhD, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2022
• Last Update Submitted That Met QC Criteria: May 10, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; radiotherapy; radiation therapy; SBRT; hypofractionation; preoperative; neoadjuvant radiation; stereotactic
• Additional Relevant MeSH Terms: Skin Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Neoplasms; Pneumonia, Viral; Pneumonia; Lung Diseases; Neoplasms by Site; Breast Diseases; COVID-19; Breast Neoplasms
• Other Study ID Numbers: 115858

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No