Immune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer

Breast Adenocarcinoma Clinical Trial

Official title:

Immune Response to Anti-HER2 Therapies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04517838
• Other study ID #: MC1937
• Secondary ID: NCI-2020-0578119
• Status: Recruiting
• Start date: July 27, 2020
• Est. completion date: July 27, 2028

Study information

• Verified date: January 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: July 27, 2028
• Est. primary completion date: July 27, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Adenocarcinoma
• Breast Neoplasms

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood and tumor tissue samples

Locations

Country	Name	City	State
United States	Mayo Clinic in Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of patients who develop HER2-specific T cell and endogenous antibody responses	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.	Up to 16 weeks
Other	Levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies	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
Other	Association between combination therapy and immunity to common breast cancer associated antigens	Descriptive statistics will be used.	Up to 16 weeks
Other	Association between HER2-specific T cell or antibody immunity and improved progression-free survival	Descriptive statistics will be used.	Up to 16 weeks
Other	Association between HER2-specific T cell or antibody immunity and improved overall survival in patients	Descriptive statistics will be used.	Up to 16 weeks
Other	Association between anti-HER2 therapy and HER2 loss and modulation of HER2-specific adaptive immune responses	Descriptive statistics will be used.	Up to 16 weeks
Other	Association between loss-of-function mutations and recurrence	Descriptive statistics will be used.	Up to 16 weeks or recurrence
Other	Association between gene expression levels and recurrence	Descriptive statistics will be used.	Up to 16 weeks or recurrence
Other	Association between Fc gamma receptor (R) or human leukocyte antigen (HLA) genotypes and ability to generate immunity	Descriptive statistics will be used.	Up to 16 weeks
Primary	HER2 specific T-cell response and clinical response	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
Primary	Antibody response and clinical response	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

External Links

•   Mayo Clinic Clinical Trials