Clinical trial NCT04517838: Immune Response to Anti-HER2 Therapies in Patients with HER2-Positive Stage I-IV Breast Cancer
Official title: Immune Response to Anti-HER2 Therapies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Adenocarcinoma
HER2-Positive Breast Carcinoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-08-18
Enrollment: 750
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Stage I-IV HER2 positive breast cancer patients

Brief summary: This study gathers information from the blood cells and tumor tissue during treatment with anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib, in patients with HER2 positive stage I-IV breast cancer who are scheduled to start anti-HER2 therapy. The information gained from this study may help researchers better understand the relation between cell response and anti-HER2 therapies.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: HER2 specific T-cell response and clinical response
timeFrame: Up to 16 weeks
measure: Antibody response and clinical response
timeFrame: Up to 16 weeks
Secondary outcomes:
Other outcomes:
measure: Proportion of patients who develop HER2-specific T cell and endogenous antibody responses
timeFrame: Up to 16 weeks
measure: Levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies
timeFrame: Up to 16 weeks
measure: Association between combination therapy and immunity to common breast cancer associated antigens
timeFrame: Up to 16 weeks
measure: Association between HER2-specific T cell or antibody immunity and improved progression-free survival
timeFrame: Up to 16 weeks
measure: Association between HER2-specific T cell or antibody immunity and improved overall survival in patients
timeFrame: Up to 16 weeks
measure: Association between anti-HER2 therapy and HER2 loss and modulation of HER2-specific adaptive immune responses
timeFrame: Up to 16 weeks
measure: Association between loss-of-function mutations and recurrence
timeFrame: Up to 16 weeks or recurrence
measure: Association between gene expression levels and recurrence
timeFrame: Up to 16 weeks or recurrence
measure: Association between Fc gamma receptor (R) or human leukocyte antigen (HLA) genotypes and ability to generate immunity
timeFrame: Up to 16 weeks
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Saranya Chumsri, MD
role: PRINCIPAL_INVESTIGATOR
References: