HKI-272 for HER2-Positive Breast Cancer and Brain Metastases

Status: Recruiting
Phase: Phase 2
Diagnosis: Breast: Metastatic
NCT ID: NCT01494662 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-344

 

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.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Beth-Israel Deaconess Medical Center, Dana Farber Cancer Institute at Faulkner Hospital, Massachusetts General Hospital

Overall PI:
Rachel Freedman, MD, Dana Farber Cancer Institute

Site-responsible Investigators:
Christina Herold, Beth Israel Deaconess Medical Center
Erica Mayer, MD, Dana-Farber Cancer Institute
Beverly Moy, MD, Massachusetts General Hospital

Contacts:
Dana-Farber Cancer Institute: Breast Cancer Nursing Team, 617-632-3478
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Patients (men or women) must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study. - Invasive primary tumor or metastatic tissue confirmation of HER2-positive status - Over-expression by immunohistochemistry (IHC) with score of 3+ (in > 30% of invasive tumor cells) AND/OR HER2 gene amplification (> 6 HER2 gene copies per nucleus or a FISH ratio [HER2 gene copies to chromosome 17 signals] of ≥ 2.0) - Patients must have measurable CNS disease, defined as at least one parenchymal brain lesion that can be accurately measured in at least one dimension with longest dimension ≥10 mm by local radiology review. Note: measurable non-CNS disease is NOT required for study participation - Prior trastuzumab and lapatinib therapy are allowed. - There is no limit to the number of previous lines of therapy (including chemotherapy, trastuzumab, and endocrine therapies) - No prior therapy with neratinib is allowed - For cohort 1, patients must have new or progressive CNS lesions, as assessed by the patient's treating physician. This includes patients who have progressed after at least one line of standard treatment for CNS disease - In cohort 2, eligible patients will include those who have CNS disease that is amenable for surgery (typically < 3 brain metastases and with planned resection by neurosurgery). These patients may include those who have received or not received previous treatment(s) for their CNS. - It is anticipated that some patients may have multiple progressive CNS lesions, one or several of which are treated with SRS or surgery with residual untreated lesions remaining. Such patients are eligible for enrollment on this study providing that at least one residual (i.e. non-SRS-treated or non-resected) lesion is measurable, as defined in Section 4.1.3. The location of the measurable lesion should be documented in the patient chart and case report form. - Patients who have had prior cranial surgery are eligible, provided that there is evidence of measurable residual or progressive lesions, and at least 2 weeks have passed since surgery. If a patient has surgical resection followed by WBRT, then there must be evidence of progressive CNS disease after the completion of WBRT. Exclusion Criteria: - Not pregnant or breastfeeding - Participants who have had chemotherapy or radiotherapy (including investigational agents) within 2 weeks prior to entering the study or those who have not recovered adequately from adverse events due to agents administered more than 4 weeks earlier (excluding alopecia). Washout from trastuzumab is not required. - Participants who are currently receiving any other investigational agents - History of allergic reactions attributed to compounds of similar chemical or biologic composition to neratinib - Concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs), including phenytoin, carbamazepine, oxcarbazepine, fosphenytoin, phenobarbital, pentobarbital, or primidone - Patients who are receiving any cancer-directed concurrent therapy, such as concurrent chemotherapy, radiotherapy, or hormonal therapy while on study. Concurrent treatment with bisphosphonates is allowed but should be started before the first dose of neratinib. - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - More than two seizures over the last 4 weeks prior to study entry - Patients with known contraindication to MRI, such as cardiac pacemaker, shrapnel, or ocular foreign body - Those with leptomeningeal metastases as the only site of CNS disease - Significant malabsorption syndrome or inability to tolerate oral medications - Any predisposing chronic condition resulting in baseline grade 2 or higher diarrhea
  • Email
  • Print
  • Share
  • Text
Highlight Glossary Terms