HKI-272 for Breast Cancer

Recruiting at17 trial locations

Overseen by Rachel 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.

Research Team

Rachel Freedman, M.D., M.P.H.

Principal Investigator

Dana-Farber Cancer Institute

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.

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.

Treatment Details

Interventions

• HKI-272 (Small Molecule Kinase Inhibitor)

Trial Overview 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.

Participant Groups

Group I: Cohort 3a/3b Active Control 1 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/4c Active Control 2 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 1 Active Control 1 Intervention

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

Group IV: Cohort 2 Active Control 1 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.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Dr. Benjamin L. Ebert

Dana-Farber Cancer Institute

Chief Executive Officer

MD from Harvard Medical School, PhD from Oxford University

Dr. Craig A. Bunnell

Dana-Farber Cancer Institute

Chief Medical Officer since 2012

MD from Harvard Medical School, MPH from Harvard School of Public Health, MBA from MIT Sloan School of Management

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Puma Biotechnology, Inc.

Industry Sponsor

Trials

58

Recruited

10,100+