RecruitingPhase 2Phase 3NCT05288777

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

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

Sponsor

University of Virginia

Enrollment

45 participants

Start Date

Jul 11, 2022

Study Type

INTERVENTIONAL

Conditions

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

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria21

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
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
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
Agreement to adhere to Lifestyle Considerations throughout study duration
Subjects taking warfarin and plan to receive capecitabine will need their anticoagulant management assessed before starting treatment.

Exclusion Criteria16

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.
Unwilling to discontinue endocrine therapy if currently taking endocrine therapy.

Interventions

DRUGT-DM1

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

DRUGCapecitabine

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

RADIATIONExternal 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.

RADIATIONExternal 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.