- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04517838
Immune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer
Immune Response to Anti-HER2 Therapies
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES I. To determine the correlation between HER2 specific T-cell response in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.
II. To determine the correlation between antibody response in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.
III. To determine the correlation between host immune response in tumor tissue in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.
EXPLORATORY OBJECTIVES:
I. To estimate the proportion of patients who develop HER2-specific T cell and endogenous antibody responses.
II. To examine within individual patients trends in levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies over the course of treatment.
III. To determine if combination therapy induces immunity to common breast cancer associated antigens (i.e. CEA, IGFBP2, and P53).
IV. To determine if induction of HER2-specific T cell or antibody immunity is associated with improved progression-free and overall survival in patients.
V. To determine if there are Fc gamma receptor (R) or HLA genotypes associated with the ability to generate immunity in response to anti-HER2 therapy.
VI. To determine whether anti-HER2 therapy induces HER2 loss and modulation of HER2-specific adaptive immune responses.
VII. To determine if loss-of-function mutations in antigen presenting genes are associated with recurrence in patients with HER2+ breast cancer.
VIII. To determine gene expression levels in tumors from patients who did not achieve pathologic complete response (pCR) that are associated with recurrence.
OUTLINE: This is an observational study. Patients are assigned to 1 of 2 cohorts.
BLOOD & TISSUE COHORT: Patients with stage I-III disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. Patients with stage IV disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of progressive disease. Patients with stage IV disease with no disease progression ≥ 2 years on the same line of therapy undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. For all patients, tissue samples from previous biopsy and/or surgical resection are also collected on study.
TISSUE-ONLY COHORT: For patients with stage I-IV disease who received or previously completed anti-HER2 therapy, tissue samples from previous biopsy and/or surgical resection are collected on study.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
-
-
Florida
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Jacksonville, Florida, United States, 32224-9980
- Recruiting
- Mayo Clinic in Florida
-
Contact:
- Clinical Trials Referral Office
- Phone Number: 855-776-0015
- Email: mayocliniccancerstudies@mayo.edu
-
Principal Investigator:
- Saranya Chumsri, M.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age >= 18 years
- Histological confirmed adenocarcinoma of the breast stage I-IV from the American Joint Committee on Cancer staging 8th edition
- Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as per the most current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline
- Provide written informed consent
- Willingness to provide blood samples for correlative research purposes
- BLOOD AND TISSUE COHORT: Scheduled to start new anti-HER2 therapy/therapies
- TISSUE-ONLY COHORT: Received or previously completed anti-HER2 therapy/therapies
Exclusion Criteria:
- Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive
- Receiving systemic steroid therapy or any other immunosuppressive therapy =< 30 days prior to registration. NOTE: Inhaled steroids, low-dose corticosteroids (e.g. equivalent to or less than oral prednisone 10 mg daily), and steroid use for primary prevention of nausea per institutional guidelines are allowed.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Observational Blood & Tissue Cohort
Patients with stage I-III disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence.
Patients with stage IV disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of progressive disease.
Patients with stage IV disease with no disease progression ≥ 2 years on the same line of therapy undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence.
For all patients, tissue samples from previous biopsy and/or surgical resection are also collected on study.
|
Undergo collection of blood and tumor tissue samples
Other Names:
|
Observational Tissue-Only Cohort
For patients with stage I-IV disease who received or previously completed anti-HER2 therapy, tissue samples from previous biopsy and/or surgical resection are collected on study.
|
Undergo collection of blood and tumor tissue samples
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HER2 specific T-cell response and clinical response
Time Frame: Up to 16 weeks
|
Defined as (1) a 2-fold or greater increase in HER2-specific T cells or HER2-specific antibodies at any point during treatment if pre-treatment levels of HER2-specific T cells or antibodies are detectable, or (2) HER2-specific T cells or HER2-specific antibodies at any point during treatment if pretreatment levels of HER-2 binding activity are non-detectable.
|
Up to 16 weeks
|
Antibody response and clinical response
Time Frame: Up to 16 weeks
|
Defined as (1) a 2-fold or greater increase in HER2-specific T cells or HER2-specific antibodies at any point during treatment if pre-treatment levels of HER2-specific T cells or antibodies are detectable, or (2) HER2-specific T cells or HER2-specific antibodies at any point during treatment if pretreatment levels of HER-2 binding activity are non-detectable.
|
Up to 16 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients who develop HER2-specific T cell and endogenous antibody responses
Time Frame: Up to 16 weeks
|
A two sided alpha=0.10
test of proportions will be used to assess whether the proportion of women who develop a HER2-specific immune response differs between the women who develop a tumor response and those who do not.
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Up to 16 weeks
|
Levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies
Time Frame: Up to 16 weeks
|
Descriptive statistics will be used to quantify T cell or antibody response within each cohort of patients, namely (neo)adjuvant vs. metastatic setting and within each anti-HER2 treatments (i.e.
trastuzumab, pertuzumab, lapatinib, or neratinib).
|
Up to 16 weeks
|
Association between combination therapy and immunity to common breast cancer associated antigens
Time Frame: Up to 16 weeks
|
Descriptive statistics will be used.
|
Up to 16 weeks
|
Association between HER2-specific T cell or antibody immunity and improved progression-free survival
Time Frame: Up to 16 weeks
|
Descriptive statistics will be used.
|
Up to 16 weeks
|
Association between HER2-specific T cell or antibody immunity and improved overall survival in patients
Time Frame: Up to 16 weeks
|
Descriptive statistics will be used.
|
Up to 16 weeks
|
Association between anti-HER2 therapy and HER2 loss and modulation of HER2-specific adaptive immune responses
Time Frame: Up to 16 weeks
|
Descriptive statistics will be used.
|
Up to 16 weeks
|
Association between loss-of-function mutations and recurrence
Time Frame: Up to 16 weeks or recurrence
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Descriptive statistics will be used.
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Up to 16 weeks or recurrence
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Association between gene expression levels and recurrence
Time Frame: Up to 16 weeks or recurrence
|
Descriptive statistics will be used.
|
Up to 16 weeks or recurrence
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Association between Fc gamma receptor (R) or human leukocyte antigen (HLA) genotypes and ability to generate immunity
Time Frame: Up to 16 weeks
|
Descriptive statistics will be used.
|
Up to 16 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Saranya Chumsri, M.D., Mayo Clinic
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MC1937 (Mayo Clinic in Florida)
- NCI-2020-05781 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 19-011040 (Other Identifier: Mayo Clinic Institutional Review Board)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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