Three Fraction Radiation to Induce Immuno-Oncologic Response

NCT03978663 | Active Not Recruiting DMC

• 1 other identifier: 112626
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with high risk breast cancers (any locally advanced breast cancer patient defined as Stages IIB-III \[excluding inflammatory breast cancer\] with stage IIA being eligible for triple negative and HER2-positive breast cancers) will receive neoadjuvant radiation to any portion of their tumour in three fractions in order to act as an immune primer. Radiation will be delivered to a portion of the tumour in three fractions. The patient will be positioned prone as per the SIGNAL 2.0 protocol. The patient will then go on to standard of care treatment (neoadjuvant chemotherapy and surgery) followed by whole-breast radiation as needed. Pathologic complete response will be the primary outcome. Immune markers will also be evaluated.

Conditions

High-Risk Cancer; Locally Advanced Breast Cancer

Keywords

locally advanced breast cancer; immune priming; radiation therapy; neoadjuvant radiation; radiotherapy; immuno-oncology

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response

  Pathologic complete response rates after neoadjuvant radiotherapy and chemotherapy will be evaluated.

  Measured at time of surgery, typically 6 months after enrollment in trial.

Secondary Outcomes (9)

• Response rates in the primary post chemotherapy by imaging

  Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery, typically 6 months after enrollment in trial.

• Response rates in the axillary nodes post chemotherapy by imaging and pathology

  Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery (imaging) and at time of surgery, typically 6 months after enrollment in trial.

• Immune priming

  Measured 14-20 days after the last dose of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy.

• Radiation toxicity

  Measured at study enrollment, at first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.

• Surgical wound healing and the overall complication rate.

  Measured at the first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.

Study Arms (1)

Neoadjuvant radiotherapy

EXPERIMENTAL

3 doses of stereotactic radiotherapy administered prior to neoadjuvant chemotherapy in high-risk breast cancers.

Radiation: Neoadjuvant radiotherapy

Interventions

Neoadjuvant radiotherapy RADIATION

Neoadjuvant radiation therapy delivered to a portion of the index tumour for high-risk breast carcinoma for immune priming prior to neoadjuvant radiation

Neoadjuvant radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any biopsy-proven locally advanced breast cancer patient defined as Stages IIB-III (excluding inflammatory breast cancer). Stage IIA is eligible for triple negative and HER2-positive breast cancers
• Invasive mammary carcinoma of any subtype excluding lobular, sarcomatous, or metaplastic subtypes, or with lobular features
• Plan to be treated with neoadjuvant chemotherapy
• Able to fit in/have MRI
• years of age or older
• Able to tolerate core needle biopsies
• Able to provide informed consent
• No evidence of metastatic disease

You may not qualify if:

• Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery
• Prior treatment for current breast cancer
• Previous radiation therapy to the same breast
• Inflammatory breast carcinoma
• Invasive lobular carcinoma or invasive mammary carcinoma with lobular, sarcomatous, or metaplastic subtypes, or with lobular features
• Recurrent breast cancer
• Bilateral breast cancer
• Evidence of distant metastatic disease
• Collagen vascular disease (particularly lupus, scleroderma, dermatomyositis, psoriatic arthritis)
• Any other malignancy at any site (except non-melanomatous skin cancer) \<5 years prior to study enrollment
• Inability to lay prone with arms above the head for extended periods of time
• Inability to fit in/have an MRI
• Inability to tolerate core needle biopsies
• Pregnant or lactating
• Under 18 years of age

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Regional Cancer Program

London, Ontario, Canada

Location

MeSH Terms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Muriel Brackstone, MD PhD

  London Health Sciences Centre/Lawson Health Research Institute

  PRINCIPAL INVESTIGATOR

• Michael Lock, MD

  London Health Sciences Centre/London Regional Cancer Program

  STUDY CHAIR

• Brian Yaremko, MD

  London Health Sciences Centre/London Regional Cancer Program

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2019
• First Posted: June 7, 2019
• Study Start: September 2, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

CA (1)