Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer (Breast53)

A Study of Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Breast Cancer Stage I; Breast Cancer Stage II; Breast Cancer Stage III
• Intervention / Treatment: Drug: T-DM1; Radiation: External Beam Radiation Therapy 1; Radiation: External Beam Radiation Therapy 0; Drug: Capecitabine

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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Song Wood; Phone Number: 4342430008; Email: stw2g@hscmail.mcc.virginia.edu

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Song Wood; Phone Number: 434-243-0008; Email: stw2g@hscmail.mcc.virginia.edu
      • Principal Investigator: Einsley Janowski, Md, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 or older
4. Diagnosis of stage I-IIIB breast cancer
5. Received neoadjuvant chemotherapy (minimum of 3 cycles) and surgical resection (lumpectomy and/or mastectomy)
6. Discovered to have residual disease at least ypT1aNx or ypTxN1mic at surgical resection
7. Candidate for adjuvant chemoradiation as part of standard clinical care
8. Planned initiation of radiation within 12 weeks of their final oncologic surgery
9. ECOG performance status ≤2
10. Adequate cardiac function, with LVEF greater or equal to 45% (only for patients who will receive TDM-1 therapy)

11. Adequate organ function per the following criteria within 21 days before the start of treatment. If a laboratory value required for study eligibility does not meet the below requirements, the value may be retested.

    • Absolute neutrophil count ≥1.5 k/uL
    • Platelets ≥100 k/uL
    • Hemoglobin ≥ 10 g/dL
    • Serum Creatinine ≤ 1.5 x ULN
    • Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4x ULN is allowed).
    • AST and ALT ≤ 2.5 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN
12. For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 6 months after the end of chemoradiation administration or until advised by their medical oncologist
13. Agreement to adhere to Lifestyle Considerations throughout study duration
14. Subjects taking warfarin and plan to receive capecitabine will need their anticoagulant management assessed before starting treatment.

Exclusion Criteria:

1. Had a mastectomy with expander placement or immediate reconstructions
2. Diagnosed with systemic lupus
3. Diagnosed with scleroderma
4. 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.
5. Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration.
6. Pathologic evidence of metastatic disease, or strong clinical/radiological evidence of metastatic disease, at the investigator's judgment.
7. Pregnancy or lactation
8. Incarceration
9. Presence of cardiac pacemaker on side of the body that is being treated unless the pacemaker can be moved prior to treatment.
10. Anthracycline exposure exceeding a cumulative doxorubicin dose of 264 mg/m2 (240 mg/m2 plus a 10% threshold)
11. Known allergic reactions to components of capecitabine or T-DM1
12. Known DPD deficiency for patients prescribed capecitabine
13. Febrile illness within a week of starting treatment
14. Incomplete healing of chest wall or breast in the treatment field within 12 weeks from surgery.
15. Known HIV or active hepatitis.
16. Unwilling to discontinue endocrine therapy if currently taking endocrine therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Her2/neu positive and lymph node positive; T-DM1/ trastuzumab emtansine infusion along with radiation to the breast or chest wall and lymph nodes	Drug: T-DM1; Dosed at 3.6 mg/kg of body weight every 3 weeks for Her2/neu+ patients for a total duration of 14 cycles.; Other Names: trastuzumab emtansine; Radiation: External Beam Radiation Therapy 1; Dose of 40 Gy in 15 fractions to either the breast or chest wall along with comprehensive nodal radiation followed by consideration of a 10 Gy in 4 fraction boost for a total duration of 15-19 days. Internal mammary nodal, dissected axilla coverage, and boost will be at the radiation oncologist's discretion.; Other Names: EBRT
Other: Her2/neu positive and lymph node negative; T-DM1/trastuzumab emtansine infusion along with radiation to the whole breast or chest wall	Drug: T-DM1; Dosed at 3.6 mg/kg of body weight every 3 weeks for Her2/neu+ patients for a total duration of 14 cycles.; Other Names: trastuzumab emtansine; Radiation: External Beam Radiation Therapy 0; Dose of 40 Gy in 15 fractions to the whole breast or chest wall followed by consideration of a 10 Gy in 4 fraction boost to the lumpectomy cavity for a total duration of 15-19 days. Internal mammary nodal, dissected axilla coverage, and boost will be at the radiation oncologist's discretion.; Other Names: EBRT
Other: Her2/neu negative and lymph node positive; oral capecitabine twice per day along with radiation to the breast or chest wall and lymph nodes	Radiation: External Beam Radiation Therapy 1; Dose of 40 Gy in 15 fractions to either the breast or chest wall along with comprehensive nodal radiation followed by consideration of a 10 Gy in 4 fraction boost for a total duration of 15-19 days. Internal mammary nodal, dissected axilla coverage, and boost will be at the radiation oncologist's discretion.; Other Names: EBRT; Drug: Capecitabine; Dosed at 825 mg/m2 +/- 150mg twice per day for a total duration of 6 months; Other Names: xeloda
Other: Her2/neu negative and lymph node negative; oral capecitabine twice per day along with radiation to the whole breast or chest wall	Radiation: External Beam Radiation Therapy 0; Dose of 40 Gy in 15 fractions to the whole breast or chest wall followed by consideration of a 10 Gy in 4 fraction boost to the lumpectomy cavity for a total duration of 15-19 days. Internal mammary nodal, dissected axilla coverage, and boost will be at the radiation oncologist's discretion.; Other Names: EBRT; Drug: Capecitabine; Dosed at 825 mg/m2 +/- 150mg twice per day for a total duration of 6 months; Other Names: xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess safety via toxicity grading	Assessment of toxicity frequency and severity using CTCAE v5.0 adverse event grading scale throughout chemoradiation treatment and follow up.	1 year
Assess feasibility via treatment delays and completion	Percent of participants completing adjuvant chemoradiation therapy and percent of participants requiring radiation or chemotherapy dose delays.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess chronic cosmetic outcomes via LENT-SOMA scale	Assessment of chronic radiation-related cosmetic outcomes (e.g. dermatitis, telangiectasia, pigmentation, and radiation fibrosis) using "Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA)" scale throughout chemoradiation treatment and follow up. Each side effect is graded on a scale of 0 to 4, with higher scores meaning more severe outcome.	1 year
Assess acute cosmetic outcomes via RTOG/EORTC scale	Assessment of overall acute radiation related skin changes using the "Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)" grading scale throughout chemoradiation treatment and follow up. Each side effect is graded on a scale of 0 to 4, with higher scores meaning more severe outcome.	1 year
Assess cosmetic outcomes via breast measurements	Measurement of breast tissue size by measuring tape/ruler.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate recurrence-free survival	Recurrence-free survival after 1 year of adjuvant chemoradiation therapy.	1 year
Describe the amount and type of immune cells via lab tests	Lab analysis (CBC w/ Differential and ELISA assays) of blood to characterize and count leukocyte populations (neutrophils, monocytes, lymphocytes) throughout adjuvant chemoradiation treatment and follow up.	1 year
Assess quality of life via RAND SF-36 patient survey	RAND SF-36 survey assesses feelings on overall health and activity level during follow up after adjuvant chemoradiation treatment.	1 year
Assess quality of life via FACT-B patient survey	Functional Assessment of Cancer Therapy- Breast (FACT-B) survey generally assess physical wellbeing, Social wellbeing, emotional wellbeing and functional well being during follow up after adjuvant chemoradiation treatment.	1 year

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Einsley Janowski, MD, PhD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: capecitabine; Chemoradiation; Chemotherapy; trastuzumab; Adjuvant; Combination treatment; Radiation; T-DM1; xeloda; Chemo
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Trastuzumab; Capecitabine; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: HSR210410

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes