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

NCT ID: NCT05288777

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-11
• Study Completion Date: 2029-12-31

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Her2/neu positive and lymph node positive

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

Group Type: OTHER

T-DM1

Intervention Type: DRUG

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

External Beam Radiation Therapy 1

Intervention Type: 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.

Her2/neu positive and lymph node negative

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

Group Type: OTHER

T-DM1

Intervention Type: DRUG

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

External Beam Radiation Therapy 0

Intervention Type: 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.

Her2/neu negative and lymph node positive

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

Group Type: OTHER

Capecitabine

Intervention Type: DRUG

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

External Beam Radiation Therapy 1

Intervention Type: 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.

Her2/neu negative and lymph node negative

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

Group Type: OTHER

Capecitabine

Intervention Type: DRUG

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

External Beam Radiation Therapy 0

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: RADIATION

Other Intervention Names

trastuzumab emtansine; xeloda; EBRT; EBRT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Einsley-Marie Janowski, MD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Einsley Janowski, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Song Wood

Role: CONTACT

stw2g@hscmail.mcc.virginia.edu

4342430008

Facility Contacts

Song Wood

Role: primary

stw2g@hscmail.mcc.virginia.edu

434 243 0008

Other Identifiers

HSR210410

Identifier Type: -

Identifier Source: org_study_id