Study on Neratinib and Capecitabine for HER2-Negative Metastatic Breast Cancer with Brain Metastases and Abnormal HER2 Activity

Sponsor: University of Rochester

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT04965064

Provider View

This clinical trial is testing the safety and effectiveness of combining the drug neratinib with chemotherapy drug capecitabine for treating breast cancer that has spread to the brain. The study focuses on patients whose cancer is HER2-negative by standard tests but shows abnormal HER2 activity according to a special test called CELsignia.

Patient Parameters

Program Overview

The study aims to evaluate if the combination of neratinib, a HER2-targeted therapy, and capecitabine, a chemotherapy drug, is safe and effective for patients with breast cancer that has spread to the brain. Although the cancer is HER2-negative by standard tests, the CELsignia test indicates abnormal HER2 activity, suggesting that the cancer might respond to HER2-targeted treatment. Neratinib works by blocking HER2 proteins that help cancer cells grow. It is approved for HER2-positive breast cancer but is considered experimental in this study for HER2-negative cases with abnormal HER2 activity.

Description

This study is investigating the combination of neratinib and capecitabine for treating breast cancer that has spread to the brain. The focus is on patients whose cancer is HER2-negative by standard tests but shows abnormal HER2 activity based on the CELsignia test. This test might predict if the cancer will respond to the treatment.

Neratinib is a drug that targets HER2 proteins, which help cancer cells grow. It is taken orally and is approved for HER2-positive breast cancer. In this study, it is being tested for HER2-negative breast cancer with abnormal HER2 activity. The study will assess the safety and effectiveness of this treatment combination.

Participants will need to meet certain criteria to join the study, including having HER2-negative breast cancer with brain metastases and abnormal HER2 activity as shown by the CELsignia test. They must also be willing to undergo a biopsy and be medically fit for the procedure. The study will involve regular monitoring and assessments to evaluate the treatment's impact.

Eligibility Criteria

Inclusion Criteria

  • Male or female, at least 18 years old.
  • Diagnosed with HER2-negative breast cancer based on the latest tumor sample.
  • For ER-positive breast cancer: must have had prior treatment with a CDK4/6 inhibitor and endocrine therapy in the metastatic setting, or if treated in the adjuvant setting and cancer recurred within 12 months, eligible without further treatment.
  • For triple-negative breast cancer: no specific prior treatment required.
  • Must have brain metastases visible on scans.
  • Able to undergo an MRI scan.
  • Must have measurable disease outside the brain that can be biopsied.
  • Willing to have a tumor biopsy.
  • Medically fit for a biopsy.
  • Expected to need systemic therapy now or in the future.
  • Able to understand the study and sign informed consent.
  • Abnormal HER2 activity as shown by the CELsignia test.
  • New or worsening brain metastases.
  • No major surgery within 10 days before joining the study.
  • Must meet specific timeframes since last treatments (e.g., chemotherapy, hormonal therapy, targeted therapy).
  • ECOG performance status of 0-2.
  • Heart function with ejection fraction ≥ 50%.
  • Recovered from previous treatment-related organ toxicities.
  • Adequate bone marrow, liver, kidney, and blood clotting function.
  • Post-menopausal, surgically sterile, or using reliable contraception during and after the study.
  • Men must use effective contraception for at least 90 days after the last dose.

Exclusion Criteria

  • Previously treated with capecitabine for current metastatic breast cancer.
  • Cancer recurred while on capecitabine or within 180 days of last dose in early-stage treatment.
  • History of other cancers, except certain skin or cervical cancers, or other solid tumors treated and no recurrence in the last 2 years.
  • Digestive issues preventing absorption of oral medication.
  • Allergic to study drugs or components.
  • Pregnant or breastfeeding.
  • Known or suspected leptomeningeal disease.
  • Bleeding or clotting disorders, or on blood thinners that increase biopsy risk.
  • Using certain medications that affect drug metabolism (CYP3A4 inhibitors/inducers).
  • Uncontrolled medical conditions affecting study participation.
  • Inflammatory bowel disease with major diarrhea component.
  • Normal HER2 activity by CELsignia test.
  • Recent whole-brain radiotherapy.
  • Uncontrolled high blood pressure or serious heart conditions.
  • Recent blood clots (within 3 months).

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