Clinical trial NCT02212860: Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Early Stage Breast Carcinoma
Keywords: neoadjuvant
radiation
breast
cancer
hypofractionation
stereotactic
preoperative
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
name: Sunnybrook Health Sciences Centre
name: Ontario Institute for Cancer Research
First posted: 2014-08-08
Enrollment: 139
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Immune priming will be measured
timeFrame: 1.5 years
measure: Angiogenesis will be measured
timeFrame: 1.5 years
measure: Proliferation markers will be measured
timeFrame: 1.5 years
measure: Hypoxia markers will be measured
timeFrame: 1.5 years
measure: Apoptosis markers will be measured
timeFrame: 1.5 years
measure: Invasion markers will be measured
timeFrame: 1.5 years
measure: Toxicity resulting from radiation treatment
timeFrame: 1.5 years
Secondary outcomes:
measure: Cosmesis of the treated breast
timeFrame: 1.5 years
measure: Disease-Free Survival
timeFrame: 8.5 years
measure: Mastectomy-Free Survival
timeFrame: 8.5 years
measure: Overall Survival
timeFrame: 8.5 years
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Cancer Program of the Lawson Health Research Institute
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Muriel Brackstone, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: