Study Evaluating Pyrotinib in Combination With Capecitabine In Patients With HER2 Positive Metastatic Breast Cancer
Study Evaluating Pyrotinib in Combination With Capecitabine In Patients With HER2 Positive Metastatic Breast Cancer
Pyrotinib is an oral tyrosine kinase inhibitor targeting both EGFR and HER-2 receptors. This
 study is designed to evaluate the safety and tolerability of Pyrotinib in combination with
 capecitabine in patients with HER2 positive metastatic breast cancer:

 To evaluate the safety and tolerability of pyrotinib, and the maximum tolerated dose (MTD) To
 determine the dose-limiting toxicity (DLT) To determine the pharmacokinetic profile of
 Pyrotinib To assess preliminary antitumor activity To determine preliminary regimen dose for
 phase II study
Inclusion Criteria:

 -  Aged ≥18 and ≤70 years.

 -  ECOG performance status of 0 to 1.

 -  Life expectancy of more than 12 weeks.

 -  At least one measurable lesion exists.(RECIST 1.1)

 -  Histologically or cytologic confirmed HER2 positive metastatic breast cancer which
 failed prior therapies.

 -  No previous treatment of capecitabin during the past 1 year.

 -  Required laboratory values including following parameters:

 ANC: ≥ 1.5 x 109/L Platelet count: ≥ 100 x 109/L Hemoglobin: ≥ 9.0 g/dL Total bilirubin: ≤
 1.5 x upper limit of normal, ULN ALT and AST: ≤ 1.5 x ULN BUN and creatine clearance rate:
 ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms

 -  Signed informed consent.

 Exclusion Criteria:

 -  Subjects with third space fluid that can not be controled by drainage or other
 methods.

 -  Steroid treatment for more than 50 days, or in need of long-term use of steroids.

 -  Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal
 absorption.

 -  Less than 4 weeks from the last radiotherapy,chemotherapy，surgery，hermone
 treatment,target therapy, or less than 6 weeks from the nitrosoureas or mitomycin
 chemotherapy.

 -  Subjects with no efficacy during the previous treatment of capecitabine.

 -  Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.

 -  Subjects who can not interrupt the using of the drugs that may cause QT prolongation
 during study.

 -  Subjects with intracranial lesions.

 -  Subjects with bone or skin as the only target lesion

 -  Treated or treating with HER2 tyrosine kinase inhibitors (TKIs) before study entry.

 -  Receiving any other antitumor therapy.

 -  Less than 4 weeks from the last clinical trial.

 -  Known history of hypersensitivity to pyrotinib、capecitabine or any of its components
 or metabolites.

 -  Ongoing infection (determined by investigator).

 -  History of immunodeficiency, including HIV-positive, suffering from other acquired,
 congenital immunodeficiency disease, or history of organ transplantation.

 -  Subjects had any heart disease, including: (1) angina; (2) requiring medication or
 clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5)
 Any heart diseases judged by investigator as unsuitable to participate in the trial.

 -  Female patients who are pregnancy, lactation or women who are of childbearing
 potential tested positive in baseline pregnancy test.

 -  Female patients of childbearing age that are reluctant to take effective contraceptive
 measures throughout the trial period.

 -  Evidence of significant medical illness that in the investigator's judgment will
 substantially increase the risk associated with the subject's participation in and
 completion of the study. Examples include, but are not limited to,hypertension, severe
 diabetes, or thyroid disease.

 -  Alcoholism, smoking (daily ≥ 5 roots) and other bad habits.

 -  Known history of neurological or psychiatric disease, including epilepsy or dementia.