a phase ib study of selatinib ditosilate tablets in patients with advanced breast cancer

Conditions: Advanced Breast Cancer

Summary: brief description: this study is designed to evaluate the safety and tolerability of oral selatinib ditosilate tablets, and explore the maximum tolerated dose (mtd) and dose-limiting toxicity in patients with advanced breast cancer.

1. to evaluate the safety and tolerability of oral selatinib ditosilate tablets, and explore the maximum tolerated dose (mtd) and dose-limiting toxicity (dlt). 2. to determine the pharmacokinetic profile of single and multi oral selatinib ditosilate tablets . 3. to determine preliminary dose and regimen for phase ii study of oral selatinib ditosilate tablets. 4. to assess preliminary antitumor activity .

Eligibility criteria:
inclusion criteria: * women aged 18-65. * patients with ecog performance status of 0 or 1. * expected life-expectancy of more than 3 months. * patients must have histologically or cytologically confirmed breast cancer. either the primary breast tumor or the metastasis must overexpress her2; acceptable methods of measurement of her2 expression include immunohistochemistry (ihc) and fluorescence in situ hybridization (fish); tumors tested by ihc must be 3+ positive for her2 overexpression immunohistochemistry ; tumors tested by fish must be positive. * prior herceptin therapy is discontinued because of disease progression or patients can not afford for herceptin therapy. * patients with at least one measurable lesion (recist1.1 criteria). * hematology： wbc≥3.5×109/l, anc≥1.5×109/l, plt≥100×109/l，hb≥90g/l; * biochemistry： serum bilirubin≤1.5 times upper limit of normal (uln),ast and alt ≤1.5 times uln; creatinine and urea nitrogen≤1.5 times uln; lvef≥50%, ecg normal, and fridericia corrected qt(qtcf)\<470ms. * patients receiving damage caused by other therapeutic has been restored, the interval more than six weeks since the last receiving nitroso or mitomycin; more than 4 weeks since last receiving radiotherapy, other cytotoxic drugs or surgery. * subjects can swallow and have normal gastrointestinal function. * female subjects should agree to take contraceptives during the study and within 6 months after the study (such as intrauterine device \[iud\], contraceptive drugs or condoms); within 7 days before they enter the study, their serum or human chorionic gonadotropin should be negative, and must be in the non-lactation period. * ability to understand and the willingness to sign a written informed consent document. exclusion criteria: * patients have uncontrolled large pleural effusion and ascites. * patients have received steroid for more than 50 days, or requiring for steroid therapy for a long time. * requirement for the therapeutic drugs prolonging qt interval(such as anti-arrhythmia drugs), and can not interrupt them. * patients with a history of symptomatic brain metastases. * patients have received small molecule targeted drug therapy of inhibition of her-2 or egfr. * patients have participated in other drug clinical research in the past 4 weeks. * pregnant or lactating women are excluded from this study. * patients with a history of allergic reactions attributed to compounds of similar chemical composition to the agents used in the study are ineligible; * patients with active infection ; * patients with cardiac disease including angina, any significant or need to be treated arrhythmia，myocardial infarction, heart failure, lvef\<45%, other heart diseases that are not suitable for participating in the study judged by investigator. * patients with other concurrent severe and/or uncontrolled medical conditions （including hypertension, severe diabetes, thyroid disease, etc.) that could cause unacceptable safety risks or compromise compliance with study requirements are ineligible. * patients with a history of mental disorders, including epilepsy or dementia are ineligible.