Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy

NCT02212860 | Completed DMC

• 1 other identifier: SIGNAL
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 1

Brief Summary

Radiation therapy after surgery to remove breast cancer improves control of the breast cancer. Standard therapy after breast conservation surgery is five to six weeks of radiation to the entire breast. This clinical trial will evaluate the effectiveness of conformal radiation therapy delivered only to the area in the breast where the lumpectomy will be performed. This study will determine if radiation therapy delivered in this manner will prevent the cancer from coming back and eliminate the need for five to six weeks of radiation. Eligible participants will be randomized to one of two arms; Arm 1 which is comprised of one neoadjuvant radiation treatment, or Arm 2 which is comprised of three neoadjuvant radiation treatments. The study will also gather information about the safety and effects (good and bad) this radiation has, the immune priming effects of this radiation, and on patient satisfaction with the appearance of the breast.

Conditions

Early Stage Breast Carcinoma

Keywords

neoadjuvant; radiation; breast; cancer; hypofractionation; stereotactic; preoperative

Outcome Measures

Primary Outcomes (7)

• Immune priming will be measured

  Immune priming effects of both treatment arms will be evaluated by quantifying tumour infiltrating lymphocytes (CD8) into tumour specimen, as well as the expression of immune markers (PDL1, Fox3) and immune panel in blood (CD4, CD8, neutrophil, and macrophage counts).

  1.5 years

• Angiogenesis will be measured

  Angiogenesis will be examined using the CD31 or VEGF-a cell markers

  1.5 years

• Proliferation markers will be measured

  Proliferation will be examined using the Ki67 marker, hypoxia will be examined using the Carbonic Anhydrase 9 (CAH IX), or HIF1/HIF2 markers, apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.

  1.5 years

• Hypoxia markers will be measured

  Hypoxia will be examined using the Carbonic Anhydrase 9 (CAH IX), or HIF1/HIF2 markers, apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.

  1.5 years

• Apoptosis markers will be measured

  Apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.

  1.5 years

• Invasion markers will be measured

  Invasion will be analyzed using the vimentin, or SDF1-a markers.

  1.5 years

• Toxicity resulting from radiation treatment

  Toxicity resulting from radiation treatment will be collected and graded according to the Common Terminology Criteria for Adverse Events, version 4.0

  1.5 years

Secondary Outcomes (4)

• Cosmesis of the treated breast

  1.5 years

• Disease-Free Survival

  8.5 years

• Mastectomy-Free Survival

  8.5 years

• Overall Survival

  8.5 years

Study Arms (2)

Single Fraction

EXPERIMENTAL

Stereotactic neoadjuvant ablative radiation give in one single dose of 21 Gy. Lumpectomy to follow within 14-20 from radiation treatment date.

Radiation: Stereotactic Body Radiation Then Surgery

Three Fractions

EXPERIMENTAL

Stereotactic neoadjuvant ablative radiation give in three doses of 10 Gy (30 Gy given in 3 fractions, one treatment every second business day). Lumpectomy to follow within 14-20 days from last radiation treatment.

Radiation: Stereotactic Body Radiation Then Surgery

Interventions

Stereotactic Body Radiation Then Surgery RADIATION

Stereotactic image-guided neoadjuvant ablative radiation (randomized to single dose of 21 Gy or three 10 Gy doses) followed by lumpectomy for early stage breast carcinoma

Also known as: Neoadjuvant radiation

Single Fraction; Three Fractions

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 50 years and postmenopausal
• Tumor size \< 3cm on pre-treatment imaging
• Any grade of disease, estrogen receptor (ER) positive
• 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 have surgery within 14-20 days of radiation therapy.
• Able to lie comfortably in the prone position with arms raised above the head for extended periods of time.

You may not qualify if:

• Previous RT to the same breast
• 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 breast conserving surgery 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

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Weill Medical College of Cornell University: collaborator
• Sunnybrook Health Sciences Centre: collaborator
• Ontario Institute for Cancer Research: collaborator

Study Sites (1)

London Regional Cancer Program of the Lawson Health Research Institute

London, Ontario, N6A 4L6, Canada

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Muriel Brackstone, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: August 8, 2014
• Study Start: April 27, 2015
• Primary Completion: April 23, 2021
• Study Completion: April 1, 2024
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)