Impact of Neoadjuvant Chemotherapy on the Peripheral Blood Immune Phenotype in Operable Breast Cancer, the ENHANCE Study

• ClinicalTrials.gov Identifier: NCT04897009
• Recruitment Status: Recruiting
• First Posted: May 21, 2021
• Last Update Posted: January 9, 2023
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Tracking Information

• First Submitted Date: May 18, 2021
• First Posted Date: May 21, 2021
• Last Update Posted Date: January 9, 2023
• Actual Study Start Date: June 9, 2021
• Estimated Primary Completion Date: May 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 18, 2021)

• Association of peripheral blood immune phenotypes with pathological complete response [ Time Frame: Up to 5 years ]
  For each of the ten unique family subtypes, and individual cell population within a histological subtype, will utilize a logistic regression model to identify those markers measured at baseline that are predictive of achieving a pathological complete response. Will also perform classification and regression trees (CART) modeling to get at the interplay of the markers (i.e. cell subtypes), which are all uniformly expressed as percentages.
• Difference of peripheral blood immune phenotypes [ Time Frame: Up to 5 years ]
  Will be assessed between patients with breast cancer and age-matched healthy controls. Will compare the average difference in the baseline marker expression between the cases and age-matched healthy controls using a two-sample t-test. The two-sample t-test will be used to test the null hypothesis of no difference in means against the alternative hypothesis that there is a difference in means; the two-sided P-value will be reported. Will also perform CART modeling as in the first co-primary objective to get at the interplay of the markers.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 18, 2021)

Changes in baseline peripheral blood immune phenotype as a consequence of neoadjuvant chemotherapy (NAC) [ Time Frame: Baseline up to 2-4 weeks post-surgery ]

Will calculate the absolute change for each of the 30 markers, including grouped by the ten unique family subsets. In this largely descriptive analysis, within each histologic subtype, the expression levels will be graphically displayed over time (e.g. plotting the median at each of the three occasions, as well as plotting the mean change from baseline at post-NAC and post-surgery; the patient-level trajectories will be superimposed. Because this is a hypothesis generating objective, all data will be graphed and tabulated and any inferential statistics calculated will be limited and should be interpreted with caution.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of Neoadjuvant Chemotherapy on the Peripheral Blood Immune Phenotype in Operable Breast Cancer, the ENHANCE Study
• Official Title: Evaluating the Impact of Neoadjuvant Chemotherapy on the Peripheral Blood Immune Phenotype in Patients With Operable Breast Cancer (ENHANCE)
• Brief Summary: This early phase I trial evaluates the impact of chemotherapy before surgery (neoadjuvant) on the peripheral blood immune phenotype in patients with operable breast cancer. Collecting blood and information from patients with breast cancer may help to understand how the immune system influences response to treatment, and how the immune system reacts to breast cancer treatment.

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate whether pre-neoadjuvant chemotherapy (NAC) peripheral blood immune phenotypes (defined by mass cytometry) are associated with pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with operable breast cancer.

II. To evaluate whether the baseline peripheral blood immune phenotype differs between patients with breast cancer and age-matched healthy controls.

SECONDARY OBJECTIVES:

I. To characterize changes in the baseline peripheral blood immune phenotype that arise as a consequence of neoadjuvant chemotherapy.

II. To create a biorepository of peripheral blood samples for future research in breast cancer, including circulating tumor deoxyribonucleic acid (ctDNA), epigenetic and functional studies.

EXPLORATORY OBJECTIVE:

I. To evaluate differences in peripheral blood immune phenotype of patients with oligometastatic breast cancer compared to patients with stage I-III breast cancer.

OUTLINE:

Patients undergo blood sample collection at baseline (prior to first NAC treatment), after taxane and prior to first dose of anthracycline/cyclophosphamide (A/C) (for patients receiving a taxane), end of NAC, 1-4 weeks and 6 months post-surgery. Patients also undergo tissue collection at 1-4 weeks and 6 months post-surgery.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood, tissue

• Sampling Method: Non-Probability Sample
• Study Population: Patients with histologically confirmed, operable, invasive breast cancer
• Condition: Invasive Breast Carcinoma

Intervention

Procedure: Biospecimen Collection

Undergo blood and tissue collection

Other Names:

• Biological Sample Collection
• Biospecimen Collected
• Specimen Collection

Study Groups/Cohorts

Basic science (biospecimen collection)

Patients undergo blood sample collection at baseline (prior to first NAC treatment), after taxane and prior to first dose of A/C (for patients receiving a taxane), end of NAC, 1-4 weeks and 6 months post-surgery. Patients also undergo tissue collection at 1-4 weeks and 6 months post-surgery.

Intervention: Procedure: Biospecimen Collection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 18, 2021): 165
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 15, 2025
• Estimated Primary Completion Date: May 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age >= 18 years
• Histologically confirmed, operable, invasive breast cancer. Note: Patients with oligometastatic breast cancer (up to 3 isolated distant metastases) will be eligible after review and approval by principal investigator (PI)
• Recommended to receive neoadjuvant systemic treatment by their primary medical oncologist and planning to receive one of the regimens
• Provide written informed consent
• Willing to return to Mayo Clinic for breast cancer surgery
• Willingness to provide mandatory blood specimens for future research on breast cancer at Mayo Clinic

Exclusion Criteria:

• Patients who have already initiated neoadjuvant chemotherapy for the current malignancy
• Inability to provide blood samples based on the judgement of the treating physician
• Inability to comply with the protocol
• Patient is pregnant or plans to become pregnant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04897009
• Other Study ID Numbers: MC200302; NCI-2021-04162 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); P50CA116201 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Roberto A Leon-Ferre; Mayo Clinic in Rochester

• PRS Account: Mayo Clinic
• Verification Date: January 2023