Clinical trial NCT05288777: Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer
Official title: A Study of Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
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
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2022-03-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-randomized assignment based on Her2/neu status and lymph node involvement
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Assess safety via toxicity grading
timeFrame: 1 year
measure: Assess feasibility via treatment delays and completion
timeFrame: 1 year
Secondary outcomes:
measure: Assess chronic cosmetic outcomes via LENT-SOMA scale
timeFrame: 1 year
measure: Assess acute cosmetic outcomes via RTOG/EORTC scale
timeFrame: 1 year
measure: Assess cosmetic outcomes via breast measurements
timeFrame: 1 year
Other outcomes:
measure: Estimate recurrence-free survival
timeFrame: 1 year
measure: Describe the amount and type of immune cells via lab tests
timeFrame: 1 year
measure: Assess quality of life via RAND SF-36 patient survey
timeFrame: 1 year
measure: Assess quality of life via FACT-B patient survey
timeFrame: 1 year
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Einsley Janowski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: