Breast CancerPhase 2NCT04965064
Trial of Neratinib Plus Capecitabine in Subjects With HER2-Negative Metastatic Breast Cancer With Brain Metastases and Abnormally Active HER2 Signaling
A Phase 2 study testing Capecitabine and Neratinib. in people with Breast Cancer, run by University of Rochester at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Capecitabine and Neratinib.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2022to 1 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- New or progressive brain metastases defined as any one of the following:
- Untreated measurable lesions in patients who have received surgery and/or stereotactic radiosurgery (SRS) to one or more other lesions.
- Residual or progressive lesions after surgery if asymptomatic.
- Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed by RANO-BM criteria or there are new lesions are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression.
- Patients who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible, but such patients must be asymptomatic and neurologically stable from their CNS metastases.
- Measurable brain metastases with at least one lesion > 5 mm in longest diameter AND is/are new or progressive lesion/s as defined by criterion B.
- Ability to obtain MRI
- No major surgery within 10 days prior to registration. Surgeries should be avoided any time after registration during the study treatment, but minor procedures like dental extractions and surgeries deemed important to maintain or improve patients' quality of life and are allowed.
- A minimum of 14 days since the last dose of chemotherapy except for the optional pre-Step 1 capecitabine. If pre-step 1 optional capecitabine was administered, then a minimum of 7 days from the last dose of Capecitabine is required before registration. There is no limit on the number of previous chemotherapy regimens for eligibility.
- A minimum of 7 days since the last dose of any hormonal therapy (no limit on the number of previous hormonal regimens for eligibility) except fulvestrant. A minimum of 28 days since the last dose of fulvestrant before registration.
- A minimum of 21 days since the last dose of targeted therapy (e.g., a CDK4/6 inhibitor, PI3kinase inhibitors, etc.)
- A minimum of 7 days since the last fraction of extracranial radiation and has recovered from any acute toxic effects of radiation therapy
- A minimum of 30 days since the last dose of any investigational cancer treatment or any immunotherapy
- ECOG performance status of 0 -2
- Left ventricular ejection fraction ≥ 50% at baseline
- Prior treatment-related major organ toxicities recovered to ≤grade 1
- Adequate bone marrow, hepatic, renal, and coagulation function
- Post-menopausal, surgically sterile, or willing to use a reliable form of contraception while on the study and for 180 days after discontinuing either study treatment. The patients that can father children are willing to use highly effective contraception for at least 90 days following last dose of either study treatment.
- Ability to understand the investigational nature of the study and sign the informed consent
Who cannot join
- 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
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- 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
- Inconclusive HER2 signaling testing by the CELsignia test on the tumor tissue
- Whole-brain radiotherapy in the prior three months
- Resting blood pressure higher than systolic of 160 and/or diastolic of 110 mmHg or poorly controlled hypertension, history of labile hypertension, or poor compliance with anti-hypertensive medication
- Serious cardiac illness or condition including, but not limited to, clinically significant congestive heart failure, high-risk uncontrolled arrhythmias, unstable angina pectoris requiring medication, or clinically significant valvular heart disease
- History of pulmonary embolus or deep vein thrombosis diagnosed within the previous three months
- Current uncontrolled medical conditions that could limit a subject's ability to undertake study therapy
- Known or suspected leptomeningeal disease
- Inflammatory bowel disease with diarrhea as a major component
- 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 1.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Rochester
Rochester, New York, 14642
Jamie Littleton, WCICTOResearch@URMC.Rochester.edu
About this study
Official title: An Open-Label Phase II Trial of Neratinib Plus Capecitabine in Subjects With HER2-Negative Metastatic Breast Cancer With Brain Metastases and Abnormally Active HER2 Signaling
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.
Read the detailed description
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. The CELsignia test results might predict whether this breast cancer type will respond to treatment with neratinib and capecitabine.
Neratinib is called a HER2-targeted therapy because it stops cancer cells from growing by targeting and blocking the HER2 proteins that help cancer cells grow. Neratinib is an oral drug approved by the U.S. Food and Drug Administration (FDA) to treat HER2-positive breast cancer. It is considered investigational in this study because your breast cancer was determined to be HER2-negative by the standard method of testing. However, the CELsignia test showed that your breast cancer cells have HER2 pathway activity that might respond to HER2-targeted treatment.
- Conditions
- Breast Cancer
- Being tested
- Capecitabine and Neratinib.
- Keywords
- HER2-negative metastatic breast cancer, Brain metastases
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Capecitabine and Neratinib. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2021
- Study start23 Sep 2022
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ajay Dhakal, University of Rochester
- Investigators
- Ajay Dhakal, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04965064
- Sponsor's protocol ID
- UBRS20139
- Status last verified
- Dec 2025
- First submitted
- 2 Jul 2021
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase II Trial of Neratinib Plus Capecitabine in Subjects With HER2-Negative Metastatic Breast Cancer With Brain Metastases and Abnormally Active HER2 Signaling
- ClinicalTrials.gov ID
- NCT04965064
- Acronym / sponsor ID
- UBRS20139
- Conditions
- Breast Cancer
- Keywords
- HER2-negative metastatic breast cancer, Brain metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- 23 Sep 2022 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 16 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. The CELsignia test results might predict whether this breast cancer type will respond to treatment with neratinib and capecitabine.
Neratinib is called a HER2-targeted therapy because it stops cancer cells from growing by targeting and blocking the HER2 proteins that help cancer cells grow. Neratinib is an oral drug approved by the U.S. Food and Drug Administration (FDA) to treat HER2-positive breast cancer. It is considered investigational in this study because your breast cancer was determined to be HER2-negative by the standard method of testing. However, the CELsignia test showed that your breast cancer cells have HER2 pathway activity that might respond to HER2-targeted treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Capecitabine and Neratinib. | Experimental | Drug: Capecitabine and Neratinib.Neratinib 240 mg PO QD Daily On-going Capecitabine 750 mg/m2 PO bid Days 1-14, 7 days off On-going |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Subjects must meet all of the following criteria to be enrolled:
- Key Criteria for Step 1 Registration:
Key exclusion criteria (24 listed)
- Subjects must NOT meet any of the following criteria to be enrolled:
- Key Criteria for Step 1:
- Normally active HER2 signaling as determined by the CELsignia test on the tumor tissue
- Inconclusive HER2 signaling testing by the CELsignia test on the tumor tissue
- Whole-brain radiotherapy in the prior three months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Capecitabine and Neratinib.Neratinib 240 mg PO QD Daily On-going Capecitabine 750 mg/m2 PO bid Days 1-14, 7 days off On-going | Drug | Experimental: Capecitabine and Neratinib. |
Primary outcome
overall survival
Time frame: 24 months
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
CNS progression free survival
Time frame: 24 months
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ajay Dhakal principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine and Neratinib. in people with Breast Cancer, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jamie Littleton ((585) 273-1507, WCICTOResearch@URMC.Rochester.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.