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

NCT05288777 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HSR210410
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Breast Cancer Stage I; Breast Cancer Stage II; Breast Cancer Stage III

Keywords

Radiation; Chemoradiation; Chemotherapy; Chemo; T-DM1; xeloda; capecitabine; Adjuvant; Combination treatment; trastuzumab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Other Outcomes (4)

• Estimate recurrence-free survival

  1 year

• Describe the amount and type of immune cells via lab tests

  1 year

• Assess quality of life via RAND SF-36 patient survey

  1 year

Study Arms (4)

Her2/neu positive and lymph node positive

OTHER

T-DM1/ trastuzumab emtansine infusion along with radiation to the breast or chest wall and lymph nodes

Drug: T-DM1; Radiation: External Beam Radiation Therapy 1

Her2/neu positive and lymph node negative

OTHER

T-DM1/trastuzumab emtansine infusion along with radiation to the whole breast or chest wall

Drug: T-DM1; Radiation: External Beam Radiation Therapy 0

Her2/neu negative and lymph node positive

OTHER

oral capecitabine twice per day along with radiation to the breast or chest wall and lymph nodes

Drug: Capecitabine; Radiation: External Beam Radiation Therapy 1

Her2/neu negative and lymph node negative

OTHER

oral capecitabine twice per day along with radiation to the whole breast or chest wall

Drug: Capecitabine; Radiation: External Beam Radiation Therapy 0

Interventions

T-DM1 DRUG

Dosed at 3.6 mg/kg of body weight every 3 weeks for Her2/neu+ patients for a total duration of 14 cycles.

Also known as: trastuzumab emtansine

Her2/neu positive and lymph node negative; Her2/neu positive and lymph node positive

Capecitabine DRUG

Dosed at 825 mg/m2 +/- 150mg twice per day for a total duration of 6 months

Also known as: xeloda

Her2/neu negative and lymph node negative; Her2/neu negative and lymph node positive

External Beam Radiation Therapy 0 RADIATION

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.

Also known as: EBRT

Her2/neu negative and lymph node negative; Her2/neu positive and lymph node negative

External Beam Radiation Therapy 1 RADIATION

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.

Also known as: EBRT

Her2/neu negative and lymph node positive; Her2/neu positive and lymph node positive

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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)
• Known allergic reactions to components of capecitabine or T-DM1
• Known DPD deficiency for patients prescribed capecitabine
• Febrile illness within a week of starting treatment
• Incomplete healing of chest wall or breast in the treatment field within 12 weeks from surgery.
• Known HIV or active hepatitis.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Einsley Janowski, MD, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Song Wood

CONTACT

4342430008; stw2g@hscmail.mcc.virginia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants, clinical research staff, and treating clinicians will be aware of arm assignment. The labels on research blood will not include the treatment arm on which the participant is assigned and this information will not be provided to lab investigators and staff.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Non-randomized assignment based on Her2/neu status and lymph node involvement

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 21, 2022
• Study Start: July 11, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)