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Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy (SIGNAL 2)

Primary Purpose

Early Stage Breast Carcinoma

Status

Active

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Stereotactic Body Radiation Then Surgery

About this trial

This is an interventional treatment trial for Early Stage Breast Carcinoma focused on measuring neoadjuvant, radiation, breast, cancer, hypofractionation, stereotactic, preoperative

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

London Regional Cancer Program of the Lawson Health Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Single Fraction

Three Fractions

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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).

Angiogenesis will be measured

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

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.

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.

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.

Invasion markers will be measured

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

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

Secondary Outcome Measures

Cosmesis of the treated breast

cosmetic result of treated breast as judged by the patient, surgeon, and radiation oncologist. Patients will self-assess cosmesis using the Modified Harvard-Harris Cosmetic Scale. The surgeon and radiation oncologist will assess cosmesis using photographs and the Modified Harvard-Harris Cosmetic Scale.

Disease-Free Survival

Disease recurrences will be recorded. Any tumor recurrence or death is considered a treatment failure.

Mastectomy-Free Survival

All surgical interventions will be recorded. Mastectomy and death will be considered treatment failures.

Overall Survival

Death from any cause is considered a treatment failure.

Full Information

NCT ID

NCT02212860

First Posted

August 5, 2014

Last Updated

May 13, 2022

Sponsor

Lawson Health Research Institute

Collaborators

Weill Medical College of Cornell University, Sunnybrook Health Sciences Centre, Ontario Institute for Cancer Research

1. Study Identification

Unique Protocol Identification Number

NCT02212860

Brief Title

Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy

Acronym

SIGNAL 2

Official Title

Clinical Trial to Evaluate Single Dose Versus Three Doses of Stereotactic Radiation Therapy (SBRT) Prior to Surgery for Early Stage Breast Carcinoma: SIGNAL 2.0 (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 2015 (undefined)

Primary Completion Date

April 2021 (Actual)

Study Completion Date

April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Lawson Health Research Institute

Collaborators

Weill Medical College of Cornell University, Sunnybrook Health Sciences Centre, Ontario Institute for Cancer Research

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Our proposal represents the convergence of several recent developments in the treatment of patients with low-risk carcinoma of the breast. For the selected subset of patients with low-risk disease, it appears that intra-operative radiotherapy with a single fraction leads to acceptable clinical outcomes in terms of local control, overall survival and toxicity. There have also been a few Phase I dose escalation trials demonstrating safety with single fraction breast radiation. In this study, we propose the delivery of radiotherapy using stereotactic body radiation therapy in two different regimens; a single 21 Gy fraction, or 3 10Gy fractions. Radiation will be delivered using Volumetric-modulated arc therapy (VMAT), planned on coregistered MRI (with a subset having a 3T PET-MRI) and CT imaging, and delivered prone. Our approach will potentially have numerous benefits, including significantly shortened treatment time, convenience and potentially reduced health care costs. It would significantly improve the quality of life of many patients. This study will also provide a unique opportunity for pathologic assessment of the impact of radiation at a microscopic level and on tumour and immune markers without the confounding impact of systemic treatments, comparing pre- to post-radiation biopsy specimens for imaging and histologic predictors of radiation sensitivity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Early Stage Breast Carcinoma

Keywords

neoadjuvant, radiation, breast, cancer, hypofractionation, stereotactic, preoperative

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

139 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single Fraction

Arm Type

Experimental

Arm Description

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

Arm Title

Three Fractions

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Stereotactic Body Radiation Then Surgery

Other Intervention Name(s)

Neoadjuvant radiation

Intervention Description

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

Primary Outcome Measure Information:

Title

Immune priming will be measured

Description

Time Frame

1.5 years

Title

Angiogenesis will be measured

Description

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

Time Frame

1.5 years

Title

Proliferation markers will be measured

Description

Time Frame

1.5 years

Title

Hypoxia markers will be measured

Description

Time Frame

1.5 years

Title

Apoptosis markers will be measured

Description

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

Time Frame

1.5 years

Title

Invasion markers will be measured

Description

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

Time Frame

1.5 years

Title

Toxicity resulting from radiation treatment

Description

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

Time Frame

1.5 years

Secondary Outcome Measure Information:

Title

Cosmesis of the treated breast

Description

Time Frame

1.5 years

Title

Disease-Free Survival

Description

Disease recurrences will be recorded. Any tumor recurrence or death is considered a treatment failure.

Time Frame

8.5 years

Title

Mastectomy-Free Survival

Description

All surgical interventions will be recorded. Mastectomy and death will be considered treatment failures.

Time Frame

8.5 years

Title

Overall Survival

Description

Death from any cause is considered a treatment failure.

Time Frame

8.5 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Muriel Brackstone, MD, PhD

Organizational Affiliation

Lawson Health Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

London Regional Cancer Program of the Lawson Health Research Institute

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 4L6

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

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Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy

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