HKI-272 for Breast Cancer

Recruiting at 17 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Enzyme-inducing antiepileptics

Disqualifiers: Pregnancy, Active infection, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks per cycle

140 Participants Needed

What You Need to Know Before You Apply

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.

Will I have to stop taking my current medications?

The trial requires a 2-week period without chemotherapy, certain targeted therapies, or radiation before starting. Hormonal therapy must be stopped during the study, but bisphosphonates can continue if started before neratinib. Some epilepsy medications are not allowed.

How is the drug HKI-272 unique in treating breast cancer?

HKI-272, also known as neratinib, is unique because it is an oral medication that irreversibly inhibits the HER2 receptor, which is often overexpressed in breast cancer, potentially offering a more targeted approach compared to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

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

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neratinib daily, with additional treatments depending on cohort, for 4-week cycles

4 weeks per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including physical exams, imaging, and blood tests

1 month after treatment completion

1 visit (in-person)

Long-term follow-up

Participants' medical conditions are tracked for up to two years post-treatment via phone or mail

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• HKI-272

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.

How Is the Trial Designed?

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+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Puma Biotechnology, Inc.

Industry Sponsor

Trials

58

Recruited

10,100+

Published Research Related to This Trial

In a study of 181 breast cancer patients, low expression of the protein p27kip1 was found in 66.9% of cases, and higher levels were associated with better disease-free survival, indicating a potential link between p27kip1 levels and tumor behavior.

Despite the correlation between p27kip1 expression and various tumor characteristics, it was not determined to be an independent prognostic factor, suggesting that while it may influence cancer progression, other factors also play significant roles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prognostic significance of cyclin-dependent kinase inhibitor p27kip1 expression in human breast cancer]. Wu, J., Shen, Z., Shao, Z.[2006]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

p27 expression as a prognostic factor of breast cancer in Taiwan. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Prognostic significance of cyclin-dependent kinase inhibitor p27kip1 expression in human breast cancer]. [2006]

5. England pubmed.ncbi.nlm.nih.gov

Brca1 inactivation induces p27(Kip1)-dependent cell cycle arrest and delayed development in the mouse mammary gland. [2006]