Three Fraction Radiation to Induce Immuno-Oncologic Response

NCT ID: NCT03978663

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-02
• Study Completion Date: 2025-07-31

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.

Detailed Description

Patients eligible for neoadjuvant chemotherapy for locally advanced stage III (non-inflammatory) breast cancer or stage IIb (triple negative or Her2+) breast cancers will be approached to participate in this single arm trial. Patients with staging investigations ruling out distant disease will be approached to participate and will undergo pre-treatment image guided core biopsy and blood samples for molecular correlative studies, followed by hypofractionated radiation (delivered prone) to entire tumor with dose constraints to skin, critical organs and contralateral breast, plus a 0.5 cm PTV. As much of the tumor that can receive planned dose of 8 Gy per fraction x 3 fractions every second day, with fall off dose to 4 Gy per fraction x 3 fractions for PTV margin. Two weeks following completion of radiation, patients will undergo a second image guided core needle biopsy of tumor and blood sample. They will then begin standard neoadjuvant chemotherapy (anthracycline and taxane based), followed by a third tissue biopsy under image guidance of any residual tumor and blood sample and then standard surgery (breast conserving or lumpectomy). This will be followed by standard whole breast radiation (50 Gy in 25 fractions). Herceptin therapy and hormonal therapy will be administered as per clinical standard when indicated. Primary outcome will be measured as pathological complete response to treatment, and secondary outcomes will include toxicity, immune markers (tumor infiltrating lymphocytes, PD-1 and PD-L1 up-regulation and changes to the circulating lymphocyte counts.

Conditions

High-Risk Cancer; Locally Advanced Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant radiotherapy

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

Group Type: EXPERIMENTAL

Neoadjuvant radiotherapy

Intervention Type: RADIATION

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

Interventions

Neoadjuvant radiotherapy

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

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. 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

2. Invasive mammary carcinoma of any subtype excluding lobular, sarcomatous, or metaplastic subtypes, or with lobular features

3. Plan to be treated with neoadjuvant chemotherapy

4. Able to fit in/have MRI

5. 18 years of age or older

6. Able to tolerate core needle biopsies

7. Able to provide informed consent

8. No evidence of metastatic disease

Exclusion Criteria

1. Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery

2. Prior treatment for current breast cancer

3. Previous radiation therapy to the same breast

4. Inflammatory breast carcinoma

5. Invasive lobular carcinoma or invasive mammary carcinoma with lobular, sarcomatous, or metaplastic subtypes, or with lobular features

6. Recurrent breast cancer

7. Bilateral breast cancer

8. Evidence of distant metastatic disease

9. Collagen vascular disease (particularly lupus, scleroderma, dermatomyositis, psoriatic arthritis)

10. Any other malignancy at any site (except non-melanomatous skin cancer) <5 years prior to study enrollment

11. Inability to lay prone with arms above the head for extended periods of time

12. Inability to fit in/have an MRI

13. Inability to tolerate core needle biopsies

14. Pregnant or lactating

15. Under 18 years of age

16. Inability or unwillingness to provide informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Muriel Brackstone, MD PhD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre/Lawson Health Research Institute

Michael Lock, MD

Role: STUDY_CHAIR

London Health Sciences Centre/London Regional Cancer Program

Brian Yaremko, MD

Role: STUDY_CHAIR

London Health Sciences Centre/London Regional Cancer Program

Locations

London Regional Cancer Program

London, Ontario, Canada

Countries

Canada

Other Identifiers

112626

Identifier Type: -

Identifier Source: org_study_id