Trial of Neratinib Plus Capecitabine in Subjects With HER2-Negative Metastatic Breast Cancer With Brain Metastases and Abnormally Active HER2 Signaling

NCT04965064 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UBRS20139
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to look at the safety and effectiveness of a HER2-targeted therapy neratinib when given with capecitabine, a chemotherapy, for breast cancer patients with brain metastases whose tumors were HER2-negative by standard tests but showed abnormal HER2 activity based on the CELsignia results.

Conditions

Breast Cancer

Keywords

HER2-negative metastatic breast cancer; Brain metastases

Outcome Measures

Primary Outcomes (2)

• overall survival

  The study will assess how long participants with HER2 negative metastatic breast cancer with brain metastasis and abnormal HER2 signalling will survive if treated with capecitabine and neratinib

  24 months

• CNS progression free survival

  The study will assess how long participants with HER2 negative metastatic breast cancer with brain metastasis and abnormal HER2 signalling will survive and also not have the cancer get worse in the brain while treated with capecitabine and neratinib

  24 months

Study Arms (1)

Experimental: Capecitabine and Neratinib.

EXPERIMENTAL

Neratinib 240 mg PO QD Daily On-going Capecitabine 750 mg/m2 PO bid Days 1-14, 7 days off On-going

Drug: Capecitabine and Neratinib.

Interventions

Capecitabine and Neratinib. DRUG

Neratinib 240 mg PO QD Daily On-going Capecitabine 750 mg/m2 PO bid Days 1-14, 7 days off On-going

Experimental: Capecitabine and Neratinib.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be enrolled:
• Male/Female
• At least 18 years of age
• Histologically confirmed HER2 negative breast cancer determined from the most recent tumor sample (primary or metastatic), as per the current American Society of Clinical Oncology and College of American Pathologists HER2 testing guidelines.
• For ER positive breast cancer patients: prior treatment with a CDK4/6 inhibitor and endocrine therapy in required in the metastatic settings. If a patient has received a CDK4/6 inhibitor plus endocrine therapy in the adjuvant settings and the cancer recurred while on the CDK4/6 inhibitor or within 12 months of the end of CDK4/6 inhibitor treatment, then the patient will eligible without getting a CDK4/6 inhibitor and endocrine therapy in the metastatic setting.
• For triple negative breast cancer patients: no specific prior anti-cancer treatment is required.
• Have radiological evidence of one or more brain metastases.
• Ability to obtain an MRI.
• Has a radiological evidence of a measurable disease (per RECIST 1.1) outside of the brain which is accessible to a biopsy
• Willing to undergo a research core biopsy of the tumor tissue
• Considered to be medically fit for undergoing a biopsy
• Subjects anticipated by the investigator to be a candidate for systemic therapy immediately or in the future.
• Ability to understand the investigational nature of the study and sign the informed consent
• Key Criteria for Step 1 Registration:
• Abnormally active HER2 signaling as determined by the CELsignia test on the tumor tissue.

You may not qualify if:

• Subjects must NOT meet any of the following criteria to be enrolled:
• Patients who have received capecitabine for the treatment of the current breast cancer in the metastatic setting
• Patients who have received capecitabine only in the perioperative setting for the primary early-stage breast cancer AND the breast cancer recurred while taking capecitabine or within 180 days of the last dose of capecitabine therapy.
• History of other malignancies other than the following: 1. adequately treated non-melanoma skin cancer, 2. curatively treated in-situ cancer of the cervix 3. other solid tumors which have been curatively treated AND no evidence of recurrence in the last 2 years.
• Gastrointestinal tract disease resulting in an inability to absorb oral medication
• Known hypersensitivity to the study drugs or their components
• Pregnant or breast-feeding
• Known or suspected leptomeningeal disease
• Known bleeding or coagulation issues, subject taking anticoagulants or having bleeding diathesis that may significantly increase the risk of bleeding during the biopsy. If the subject is on anticoagulation, perioperative management of anticoagulation should be done per institutional practice.
• Chronic and concomitant use of strong or moderate CYP3A4 inhibitors and strong or moderate CYP3A4 inducers. These drugs should be stopped at least 14 days prior to registration to Step 0.
• Current uncontrolled medical conditions that could limit a subject's ability to undertake study therapy
• Inflammatory bowel disease with diarrhea as a major component
• Key Criteria for Step 1:
• Subjects must NOT meet any of the following criteria to be enrolled:
• Normally active HER2 signaling as determined by the CELsignia test on the tumor tissue

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

Capecitabine; neratinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ajay Dhakal

  University of Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jamie Littleton

CONTACT

(585) 273-1507; WCICTOResearch@URMC.Rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor - Department of Medicine , Hematology/Oncology (SMD)

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 16, 2021
• Study Start: September 23, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

US (1)