What side effects are associated with this type of intervention?

Common side effects of HER2-targeted therapies like Neratinib and Lapatinib include diarrhea, nausea, rash, and fatigue. Capecitabine, a chemotherapy agent, often causes hand-foot syndrome, diarrhea, nausea, and fatigue. Combining these treatments can lead to overlapping toxicities, primarily gastrointestinal issues such as diarrhea and nausea, as well as skin-related side effects like rash and hand-foot syndrome.

What prior FDA approvals exist?

Several FDA-approved treatments for breast cancer involve HER2-targeted therapies and chemotherapies. Trastuzumab (Herceptin) is a well-known HER2-targeted therapy often used in combination with chemotherapy. T-DM1 (ado-trastuzumab emtansine) is another HER2-targeted therapy approved for patients who have previously received trastuzumab and a taxane. Additionally, the combination of Tucatinib, Capecitabine, and Trastuzumab has shown improved progression-free survival and overall survival in patients with HER2-positive metastatic breast cancer. Neratinib, another HER2-targeted therapy, is being studied in combination with Capecitabine for its efficacy in treating breast cancer with brain metastases.

What other types of research exist?

Promising alternatives to Neratinib and Capecitabine for breast cancer patients include: 1) Tucatinib combined with Trastuzumab and Capecitabine, which has shown efficacy in treating HER2-positive breast cancer with brain metastases. 2) Trastuzumab Deruxtecan, which has demonstrated significant antitumor activity and safety in HER2-positive breast cancer patients, including those with brain metastases. 3) Trastuzumab Emtansine (T-DM1), which has been effective in patients with HER2-positive metastatic breast cancer and central nervous system metastases.

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Antimetabolite

Neratinib + Capecitabine for Breast Cancer

Phase 2

Recruiting

Led By Ajay Dhakal

Research Sponsored by University of Rochester

Eligibility Criteria Checklist

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

Must have

At least 18 years of age

Prior treatment-related major organ toxicities recovered to ≤grade 1

Must not have

Whole-brain radiotherapy in the prior three months for Step 1

Serious cardiac illness or condition for Step 1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of neratinib and capecitabine for breast cancer patients with brain metastases. These patients' tumors did not show HER2 activity with usual tests but did with a special test, suggesting they might benefit from this treatment. Neratinib blocks growth proteins in cancer cells, while capecitabine kills them. Neratinib is approved for use in combination with capecitabine for advanced HER2-positive breast cancer.

Who is the study for?

This trial is for adults with HER2-negative breast cancer that has spread to the brain, showing abnormal HER2 activity. Candidates must have measurable disease, be fit for a biopsy, and not have had certain treatments recently. They should not be pregnant or breastfeeding and must use reliable contraception.

What is being tested?

The study tests the combination of Neratinib (a targeted therapy) and Capecitabine (chemotherapy) in patients whose tumors are HER2-negative but show unusual HER2 activity. It aims to assess safety and effectiveness specifically for brain metastases from breast cancer.

What are the potential side effects?

Potential side effects include diarrhea, liver issues, hand-foot syndrome (redness/swelling/pain on palms/soles), nausea, vomiting, fatigue, mouth sores. Heart problems could also occur due to Neratinib.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My side effects from previous treatments have mostly gone away.

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I understand this study is experimental and I can sign the consent form.

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My breast cancer is confirmed to be HER2 negative.

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I have a tumor outside my brain that can be biopsied.

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I am able to get out of my bed or chair and move around.

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It has been over 30 days since my last experimental cancer treatment or immunotherapy.

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My cancer has spread to my brain recently or is getting worse.

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My tumor shows abnormal HER2 activity based on the CELsignia test.

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I am willing to have a biopsy for research purposes.

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I have a new or growing brain tumor larger than 5 mm.

Exclusion Criteria

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

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I have not had whole-brain radiotherapy in the last 3 months.

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I have a serious heart condition.

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I have been treated with capecitabine for my breast cancer that has spread.

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I cannot absorb pills due to my stomach or intestine condition.

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My blood pressure is often above 160/110 mmHg, or I struggle to control it with medication.

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I am not taking any strong or moderate drugs that affect enzyme CYP3A4.

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My HER2 test results were unclear.

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I have or might have cancer spread to the lining of my brain and spinal cord.

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My tumor shows normal HER2 activity.

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I have inflammatory bowel disease with significant diarrhea.

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I have bleeding problems or take blood thinners that could make a biopsy risky.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

CNS progression free survival

overall survival

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: Experimental: Capecitabine and Neratinib.Experimental Treatment1 Intervention

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

0 / 22Eligibility 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

HER2-targeted therapies, like Neratinib, inhibit the HER2 receptor, which is often overexpressed in certain breast cancers, thereby slowing or stopping tumor growth. Capecitabine, a chemotherapy drug, is converted into 5-fluorouracil (5-FU) in the body, disrupting DNA synthesis and preventing cancer cell proliferation. These mechanisms are vital for tailoring treatment to the specific cancer type, enhancing effectiveness, and minimizing adverse effects for breast cancer patients.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.New drugs for breast cancer.