HKI-272 for Breast Cancer

Recruiting in Palo Alto (17 mi)

+17 other locations

Overseen byRachel Freedman, M.D., M.P.H.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Dana-Farber Cancer Institute

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?The purpose of this research study is to determine how well neratinib works in treating breast cancer that has spread to the brain. Neratinib is a recently discovered oral drug that may stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2). In this research study, the investigators are looking to see how well neratinib works to decrease the size of or stabilize breast cancer that has spread to the brain. The investigators are also looking at how previous treatments have affected your thinking (or cognition) and how much neratinib reaches the central nervous system.

Eligibility Criteria

This trial is for adults with invasive breast cancer that has spread to the brain (HER2-positive). Participants must have measurable brain lesions, not be on certain treatments like neratinib before, and can't be taking concurrent cancer therapies. Pregnant or breastfeeding individuals, those with specific medical conditions or allergies to similar drugs, and patients who cannot tolerate oral medications are excluded.

Inclusion Criteria

No increase in corticosteroid dose in the week prior to baseline brain MRI.

No prior therapy with neratinib is allowed.

For cohort 1, you need to have a brain lesion that can be measured and is at least 10 millimeters long according to local radiology review. It's okay if you don't have measurable non-brain disease for this study.

+10 more

Exclusion Criteria

You are receiving other treatments for cancer at the same time as this study, except for certain bone-strengthening medications.

If you have a long-term condition that causes moderate or severe diarrhea, you cannot participate.

Pregnant or breastfeeding individuals are excluded from the study.

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Participant Groups

The study tests how well neratinib works on breast cancer in the brain. It's an oral drug blocking proteins involved in cancer cell growth. The trial examines its effect on tumor size/stability and cognitive function impact while monitoring how much reaches the central nervous system.

4Treatment groups

Active Control

Group I: Cohort 3a/3bActive Control1 Intervention

Cohort 3a will be made up of participants with No Prior Lapatinib Treatment. They will receive Neratinib 240mg Orally daily and 750mg/m2 Capecitabine twice per day for 14 days followed by 7 days rest. Cohort 3b will be made of of participants with Prior Lapatinib Treatment. Cohort 3b participants will receive Neratinib 240mg Orally daily and 750mg/m2 Capecitabine twice per day for 14 days followed by 7 days rest.

Group II: Cohort 4a/4b/4cActive Control2 Interventions

Cohort 4a will be made up of participants with previously untreated brain metastases. They will receive Neratinib 160mg Orally daily and T-DM1 3.6mg/kg IV every 3 weeks. Cohort 4b will be made up of participants with progressive brain metastases. They will receive Neratinib 160mg Orally daily and T-DM1 3.6mg/kg IV every 3 weeks. Cohort 4c will be made up of participants with progressive brain metastases and prior T-DM1. They will receive Neratinib 160mg Orally daily and T-DM1 3.6mg/kg IV every 3 weeks.

Group III: Cohort 1Active Control1 Intervention

Patients With Progressive Brain Metastases Intervention: HKI-272 (Neratinib)340 mg orally, once daily.

Group IV: Cohort 2Active Control1 Intervention

Patients Who Are Candidates For Craniotomy. Intervention: HKI-272 (Neratinib) 240 mg orally, once daily. Surgical resection (biopsy). Neratinib concentrations from craniotomy specimen, CSF, plasma Neratinib.