A Study of Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- T-DM1
- Conditions
- Breast Cancer
- Sponsor
- University of Virginia
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Assess safety via toxicity grading
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The goal of this study is to evaluate the safety and effectiveness of adjuvant chemoradiation therapy in high-risk breast cancer patients who had received neoadjuvant chemotherapy before their lumpectomy and/or mastectomy and were found to have residual disease. As well as examine the effects of this treatment combination on the immune system.
Detailed Description
Breast cancer is often treated with a combination of surgery, chemotherapy and radiation. In patients with advanced breast cancer, (neoadjuvant) chemotherapy is often given prior to surgical removal (lumpectomy and/or mastectomy). Neoadjuvant chemotherapy has been consistently shown to down-stage primary breast tumors and convert positive underarm lymph nodes to pathologically negative nodes. Residual disease discovered after receiving neoadjuvant chemotherapy indicates an increased risk for recurrence and poor overall survival. The combination of concurrent chemotherapy and radiation after surgery (adjuvant chemoradiation) may improve local and distant recurrence outcomes in high risk breast cancer patients. Chemoradiation is a standard treatment for many cancers and is universally associated with improvements in local recurrence, however, it has not historically been given as post-surgery breast cancer treatment. The study will evaluate the safety, feasibility, and effectiveness of chemoradiation therapy in high-risk breast cancer patients. Radiation has been associated with various effects on immune cells. The study will also examine the effects of this combination on the immune cells. Participants on this trial will be treated (per approved clinical guidelines) with capecitabine or Trastuzumab emtansine (T-DM1) depending on Her2 status while receiving radiation at the same time. Participants will have their blood drawn at various timepoints during treatment and follow up. Participants will also be asked to complete surveys asking about overall health and wellbeing.
Investigators
Einsley-Marie Janowski, MD
Assistant Professor
University of Virginia
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, aged 18 or older
- •Diagnosis of stage I-IIIB breast cancer
- •Received neoadjuvant chemotherapy (minimum of 3 cycles) and surgical resection (lumpectomy and/or mastectomy)
- •Discovered to have residual disease at least ypT1aNx or ypTxN1mic at surgical resection
- •Candidate for adjuvant chemoradiation as part of standard clinical care
- •Planned initiation of radiation within 12 weeks of their final oncologic surgery
- •ECOG performance status ≤2
- •Adequate cardiac function, with LVEF greater or equal to 45% (only for patients who will receive TDM-1 therapy)
Exclusion Criteria
- •Had a mastectomy with expander placement or immediate reconstructions
- •Diagnosed with systemic lupus
- •Diagnosed with scleroderma
- •Diagnosed with a genetic mutation associated with increased sensitivity to radiation (e.g. ataxia-telangectasias (AT)). AT heterozygotes without known radiation sensitivity may be included.
- •Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration.
- •Pathologic evidence of metastatic disease, or strong clinical/radiological evidence of metastatic disease, at the investigator's judgment.
- •Pregnancy or lactation
- •Incarceration
- •Presence of cardiac pacemaker on side of the body that is being treated unless the pacemaker can be moved prior to treatment.
- •Anthracycline exposure exceeding a cumulative doxorubicin dose of 264 mg/m2 (240 mg/m2 plus a 10% threshold)
Arms & Interventions
Her2/neu positive and lymph node positive
T-DM1/ trastuzumab emtansine infusion along with radiation to the breast or chest wall and lymph nodes
Intervention: T-DM1
Her2/neu positive and lymph node positive
T-DM1/ trastuzumab emtansine infusion along with radiation to the breast or chest wall and lymph nodes
Intervention: External Beam Radiation Therapy 1
Her2/neu positive and lymph node negative
T-DM1/trastuzumab emtansine infusion along with radiation to the whole breast or chest wall
Intervention: T-DM1
Her2/neu positive and lymph node negative
T-DM1/trastuzumab emtansine infusion along with radiation to the whole breast or chest wall
Intervention: External Beam Radiation Therapy 0
Her2/neu negative and lymph node positive
oral capecitabine twice per day along with radiation to the breast or chest wall and lymph nodes
Intervention: Capecitabine
Her2/neu negative and lymph node positive
oral capecitabine twice per day along with radiation to the breast or chest wall and lymph nodes
Intervention: External Beam Radiation Therapy 1
Her2/neu negative and lymph node negative
oral capecitabine twice per day along with radiation to the whole breast or chest wall
Intervention: Capecitabine
Her2/neu negative and lymph node negative
oral capecitabine twice per day along with radiation to the whole breast or chest wall
Intervention: External Beam Radiation Therapy 0
Outcomes
Primary Outcomes
Assess safety via toxicity grading
Time Frame: 1 year
Assessment of toxicity frequency and severity using CTCAE v5.0 adverse event grading scale throughout chemoradiation treatment and follow up.
Assess feasibility via treatment delays and completion
Time Frame: 1 year
Percent of participants completing adjuvant chemoradiation therapy and percent of participants requiring radiation or chemotherapy dose delays.
Secondary Outcomes
- Assess chronic cosmetic outcomes via LENT-SOMA scale(1 year)
- Assess acute cosmetic outcomes via RTOG/EORTC scale(1 year)
- Assess cosmetic outcomes via breast measurements(1 year)