What is the mechanism of action of this treatment?

Neratinib is a tyrosine kinase inhibitor that targets the HER2 receptor, disrupting cell signaling pathways that promote cancer cell growth and survival. Capecitabine is a chemotherapy drug that inhibits DNA synthesis, leading to cancer cell death. These mechanisms are important for breast cancer patients as they help in selecting targeted therapies that can effectively manage their specific type of cancer, potentially improving outcomes and reducing side effects.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as Tyrosine Kinase Inhibitors (TKIs) targeting HER2 (e.g., Neratinib) and chemotherapies that inhibit DNA synthesis (e.g., Capecitabine), have several known side effects. Neratinib is frequently associated with diarrhea, which can be managed with prophylactic treatment. Other side effects may include nausea, vomiting, fatigue, and liver enzyme abnormalities. Capecitabine, a chemotherapy drug, commonly causes hand-foot syndrome, diarrhea, nausea, vomiting, and fatigue. Both treatments can lead to gastrointestinal disturbances and require careful management to mitigate these adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer, including trastuzumab (Herceptin), pertuzumab (Perjeta), and ado-trastuzumab emtansine (T-DM1), which are HER2-targeted therapies. Trastuzumab is often used in combination with chemotherapy, while pertuzumab is typically combined with trastuzumab and docetaxel. T-DM1 is an antibody-drug conjugate used for patients who have previously received trastuzumab and a taxane. Capecitabine (Xeloda), a chemotherapy agent that inhibits DNA synthesis, is also FDA-approved and is often used in combination with other drugs like lapatinib or trastuzumab for advanced breast cancer. Neratinib, another HER2-targeted tyrosine kinase inhibitor, is approved for extended adjuvant treatment following trastuzumab-based therapy.

What other types of research exist?

Promising alternatives to Neratinib and Capecitabine for breast cancer treatment include: 1) Tucatinib, a tyrosine kinase inhibitor that has shown benefits in progression-free survival and overall survival when combined with trastuzumab and capecitabine. 2) Trastuzumab deruxtecan, an antibody-drug conjugate that has demonstrated high efficacy in HER2-positive metastatic breast cancer. 3) Pyrotinib, another tyrosine kinase inhibitor effective in HER2-mutant advanced lung adenocarcinoma, which may have potential in breast cancer. 4) Abemaciclib, a CDK4/6 inhibitor, in combination with trastuzumab and possibly fulvestrant, which has shown promise in hormone receptor-positive, HER2-positive advanced breast cancer.

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Anti-metabolites

Capecitabine + Neratinib for Breast Cancer

Phase 1 & 2

Waitlist Available

Led By Chau Dang, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) status of 0 to 1

Histologically confirmed MBC, current stage IV

Must not have

QTc interval >450 ms for men or 470 ms for women, or known history of QTc prolongation or Torsades de Pointes

Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety of combining two drugs, neratinib and capecitabine, in a new dosing schedule for patients with advanced breast cancer. The goal is to find out if this new schedule is safer and more effective. Neratinib blocks proteins that help cancer grow, and capecitabine stops cancer cells from multiplying.

Who is the study for?

This trial is for adults with stage IV HER2-positive metastatic breast cancer who've had trastuzumab-based therapy. They can have up to four prior chemo treatments in the metastatic setting but not neratinib with capecitabine. Stable brain lesions are okay, and they must have a good heart function (LVEF ≥50%) and be able to perform daily activities (ECOG 0-1). Women must use effective contraception.

What is being tested?

The study tests the safety of neratinib combined with capecitabine at different doses in patients with advanced breast cancer. Capecitabine is FDA-approved; neratinib isn't yet approved for this use. The focus is on whether changing the dosing schedule can improve safety compared to standard schedules.

What are the potential side effects?

Potential side effects include diarrhea, liver issues, blood cell count changes, fatigue, nausea, hand-foot syndrome from capecitabine, and possible heart problems or severe allergic reactions due to neratinib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can carry out all my daily activities without help.

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My breast cancer is confirmed to be at stage IV.

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My cancer shows high levels of HER2.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart's electrical cycle is longer than normal or I've had specific heart rhythm issues.

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I do not have any severe heart conditions or recent heart attacks.

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I've had high doses of specific chemotherapy drugs.

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I had radiation therapy less than 14 days before starting the trial treatment.

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I have a long-term stomach or bowel problem that causes serious diarrhea.

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I have a known deficiency in the enzyme dihydropyrimidine dehydrogenase.

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I am allergic to 5-fluorouracil or similar drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: capecitabine 7/7 with neratinibExperimental Treatment3 Interventions

In the phase I portion of the study, a 3+3 design will be used. Once the MTD is reached, the phase II portion will enroll up to 24 patients. Capecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Neratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Patients will be seen on Day 1 of each cycle (+/- 3 days). The MD has been determined as 240mg of neratinib and 1000mg BID of capecitabine.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Capecitabine

2013

Completed Phase 3

~4280

Neratinib

2014

Completed Phase 2

~1970

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Neratinib is a tyrosine kinase inhibitor that targets the HER2 receptor, disrupting cell signaling pathways that promote cancer cell growth and survival. Capecitabine is a chemotherapy drug that inhibits DNA synthesis, leading to cancer cell death. These mechanisms are important for breast cancer patients as they help in selecting targeted therapies that can effectively manage their specific type of cancer, potentially improving outcomes and reducing side effects.

The Clinical Efficacy and Safety of Neratinib in Combination with Capecitabine for the Treatment of Adult Patients with Advanced or Metastatic HER2-Positive Breast Cancer.Neratinib for the treatment of breast cancer.Successful treatment of leptomeningeal metastases from breast cancer using the combination of trastuzumab and capecitabine: a case report.