Capecitabine and Neratinib in Treating Patients with HER2 Positive Stage IV Breast Cancer
Inclusion Criteria
- Histologically confirmed metastatic breast cancer (MBC), current stage IV
- Documented HER2 overexpression (immunohistochemistry [IHC] 3+ or gene-amplified tumor with fluorescence in situ hybridization [FISH] ratio of >= 2.0)
- For phase Ib, any line of prior treatments is permitted including prior neratinib and capecitabine
- For phase II, up to 4 prior chemotherapy-based treatments are allowed; patients must have had prior trastuzumab-based therapy; prior neratinib treatment is not permitted; prior capecitabine is allowed, if not combined with neratinib
- Measurable or non-measurable disease is permitted as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for phase 1b; for phase 2, patients must have measurable disease as defined in RECIST v1.1
- Left ventricular ejection fraction (LVEF) >= 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO)
- Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
- White blood cell (WBC) count of >= 3000/ul
- Absolute neutrophil count (ANC) >= 1000/ul
- Platelets >= 50,000/ul
- Hemoglobin >= 8.0 g/dl
- Bilirubin =< 1.5 mg/dl
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN) (=< 5.0 x ULN if liver metastases are involved)
- Creatinine =< 1.5 mg/dl
- Patients with “treated and stable” brain lesions of a duration of >= 2 months may be enrolled
- Negative beta-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause
- Women of childbearing potential must agree and commit to the use of a highly effective method of contraception as determined to be acceptable by the investigator, from the time of informed consent until 28 days after the last dose of the investigational product; men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after last dose of investigational products
- Provide written, informed consent to participate in the study and follow the study procedures
Exclusion Criteria
- Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
- Received prior therapy resulting in a cumulative epirubicin dose > 900 mg/m^2 or cumulative doxorubicin dose > 450 mg/m^2; if another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 450 mg/m^2 doxorubicin
- Any major surgery =< 28 days prior to the initiation of investigational products, or received anti-cancer therapy (including chemotherapy, biological therapy, hormonal therapy, investigational agents, or other anti-cancer therapy) administered =< 14 days prior to the initiation of investigational products
- Received radiation therapy =< 14 days prior to initiation of investigational products
- Corrected QT (QTc) interval > 450 ms for men or 470 ms for women, or known history of QTc prolongation or Torsades de Pointes
- Active hepatitis B or C
- Active infection or unexplained fever > 38.5 degrees Celsius (C) (> 101.3 degrees Fahrenheit [F]) within 2 weeks prior to enrollment
- Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn’s disease, malabsorption, or grade >= 2 diarrhea of any etiology screening)
- Known dihydropyrimidine dehydrogenase deficiency
- Known hypersensitivity to 5-fluorouracil or to any component of the investigational products or compounds of similar chemical composition
- Pregnant patients or currently breast-feeding
Connecticut
Hartford
Florida
Miami
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
Pennsylvania
Allentown
PRIMARY OBJECTIVES:
I. To establish the safety and tolerability of capecitabine 7/7 and neratinib. (Phase Ib)
II. To assess for efficacy of capecitabine 7/7 and neratinib. (Phase II)
SECONDARY OBJECTIVES:
I. To evaluative safety and tolerability. (Phase II)
II. To assess for progression-free survival of capecitabine 7/7 and neratinib. (Phase II)
EXPLORATORY OBJECTIVES:
I. To collect research blood (i.e.: cell-free deoxyribonucleic acid [cfDNA]) to correlate with the response during treatment. (Phase II)
II. To assess quality of life while on the treatment with periodic questionnaires. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of capecitabine followed by a phase II study.
Patients receive neratinib orally (PO) once daily (QD) on days 1-28 and capecitabine PO every 12 hours (Q12H) on days 1-7 and 15-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Trial Phase Phase I/II
Trial Type Treatment
Lead Organization
Memorial Sloan Kettering Cancer Center
Principal Investigator
Chau Thanh Dang
- Primary ID 17-585
- Secondary IDs NCI-2017-02448
- Clinicaltrials.gov ID NCT03377387