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

Breast Cancer Clinical Trial

— Breast53  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05288777
• Other study ID #: HSR210410
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 11, 2022
• Est. completion date: October 2026

Study information

• Verified date: July 2023
• Source: University of Virginia
• Contact: Song Wood
• Phone: 4342430008
• Email: stw2g[@]hscmail.mcc.virginia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: October 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Stage I
• Breast Cancer Stage II
• Breast Cancer Stage III
• Breast Neoplasms

Intervention

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

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.
• 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.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Estimate recurrence-free survival	Recurrence-free survival after 1 year of adjuvant chemoradiation therapy.	1 year
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Assess cosmetic outcomes via breast measurements	Measurement of breast tissue size by measuring tape/ruler.	1 year