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Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer (Breast53)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05288777
Recruitment Status : Not yet recruiting
First Posted : March 21, 2022
Last Update Posted : April 19, 2022
Sponsor:
Information provided by (Responsible Party):
Einsley-Marie Janowski, MD, University of Virginia

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Breast Cancer Stage I Breast Cancer Stage II Breast Cancer Stage III Drug: T-DM1 Drug: Capecitabine Radiation: External Beam Radiation Therapy 0 Radiation: External Beam Radiation Therapy 1 Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Non-randomized assignment based on Her2/neu status and lymph node involvement
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: A Study of Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer
Estimated Study Start Date : May 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : October 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Her2/neu positive and lymph node positive
T-DM1/ trastuzumab emtansine infusion along with radiation to the breast or chest wall and lymph nodes
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.
Other Name: trastuzumab emtansine

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.
Other Name: EBRT

Her2/neu positive and lymph node negative
T-DM1/trastuzumab emtansine infusion along with radiation to the whole breast or chest wall
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.
Other Name: trastuzumab emtansine

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.
Other Name: EBRT

Her2/neu negative and lymph node positive
oral capecitabine twice per day along with radiation to the breast or chest wall and lymph nodes
Drug: Capecitabine
Dosed at 825 mg/m2 +/- 150mg twice per day for a total duration of 6 months
Other Name: xeloda

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.
Other Name: EBRT

Her2/neu negative and lymph node negative
oral capecitabine twice per day along with radiation to the whole breast or chest wall
Drug: Capecitabine
Dosed at 825 mg/m2 +/- 150mg twice per day for a total duration of 6 months
Other Name: xeloda

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.
Other Name: EBRT




Primary Outcome Measures :
  1. Assess safety via toxicity grading [ Time Frame: 1 year ]
    Assessment of toxicity frequency and severity using CTCAE v5.0 adverse event grading scale throughout chemoradiation treatment and follow up.

  2. Assess feasibility via treatment delays and completion [ Time Frame: 1 year ]
    Percent of participants completing adjuvant chemoradiation therapy and percent of participants requiring radiation or chemotherapy dose delays.


Secondary Outcome Measures :
  1. Assess chronic cosmetic outcomes via LENT-SOMA scale [ Time Frame: 1 year ]
    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.

  2. Assess acute cosmetic outcomes via RTOG/EORTC scale [ Time Frame: 1 year ]
    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.

  3. Assess cosmetic outcomes via breast measurements [ Time Frame: 1 year ]
    Measurement of breast tissue size by measuring tape/ruler.


Other Outcome Measures:
  1. Estimate recurrence-free survival [ Time Frame: 1 year ]
    Recurrence-free survival after 1 year of adjuvant chemoradiation therapy.

  2. Describe the amount and type of immune cells via lab tests [ Time Frame: 1 year ]
    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.

  3. Assess quality of life via RAND SF-36 patient survey [ Time Frame: 1 year ]
    RAND SF-36 survey assesses feelings on overall health and activity level during follow up after adjuvant chemoradiation treatment.

  4. Assess quality of life via FACT-B patient survey [ Time Frame: 1 year ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 k/uL
    • Platelets ≥100 k/uL
    • Hemoglobin ≥ 9 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

Exclusion Criteria:

  1. Had a mastectomy with expander placement or immediate implant 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-telangiectasias (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. Known allergic reactions to components of capecitabine or T-DM1
  11. Known DPD deficiency for patients prescribed capecitabine
  12. Febrile illness within a week of starting treatment
  13. Incomplete healing of chest wall or breast in the treatment field within 12 weeks from surgery.
  14. Known HIV or active hepatitis.
  15. Unwilling to discontinue endocrine therapy if currently taking endocrine therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05288777


Contacts
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Contact: Song Wood 4342430008 stw2g@hscmail.mcc.virginia.edu
Contact: Janowski

Locations
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United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
Contact: Song Wood    434-243-0008    stw2g@hscmail.mcc.virginia.edu   
Principal Investigator: Einsley Janowski, Md, PhD         
Sponsors and Collaborators
University of Virginia
Investigators
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Principal Investigator: Einsley Janowski, MD, PhD University of Virginia
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Responsible Party: Einsley-Marie Janowski, MD, Assistant Professor, University of Virginia
ClinicalTrials.gov Identifier: NCT05288777    
Other Study ID Numbers: HSR210410
First Posted: March 21, 2022    Key Record Dates
Last Update Posted: April 19, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Einsley-Marie Janowski, MD, University of Virginia:
Radiation
Chemoradiation
Chemotherapy
Chemo
T-DM1
xeloda
capecitabine
Adjuvant
Combination treatment
trastuzumab
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Trastuzumab
Ado-Trastuzumab Emtansine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators