A Phase Ib Study of Selatinib Ditosilate Tablets in Patients With Advanced Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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To evaluate the safety and tolerability of oral Selatinib Ditosilate Tablets, and explore the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). To determine the pharmacokinetic profile of single and multi oral Selatinib Ditosilate Tablets . To determine preliminary dose and regimen for phase II study of oral Selatinib Ditosilate Tablets. To assess preliminary antitumor activity .

Official Title
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A Phase Ib Study to Evaluate the Tolerability and Pharmacokinetics of Selatinib Ditosilate Tablets in Patients With Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: selatinib ditosilate tablets


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selatinib Ditosilate Tablets<br>Selatinib Ditosilate either at 450,750,1000,1250mg, p.o. once daily | Drug: selatinib ditosilate tablets<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity(DLT) |  | 21 days | 
| Maximum tolerated dose(MTD) |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Selatinib Ditosilate pharmacokinetic parameters , include AUC, Cmax, Tmax, and t1/2 | 21 days | 
| Pharmacodynamics | The response of Salatinib Ditosilate on tumor measured by CT or MRI. | 7 weeks |