A Phase Ib Study of Selatinib Ditosilate Tablets in Patients With Advanced Breast Cancer
Phase 1
- Conditions
- Advanced Breast Cancer
- Interventions
- Drug: selatinib ditosilate tablets
- Registration Number
- NCT01931943
- Lead Sponsor
- Qilu Pharmaceutical Co., Ltd.
- Brief 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.
- Detailed Description
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 .
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 24
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Selatinib Ditosilate Tablets selatinib ditosilate tablets Selatinib Ditosilate either at 450,750,1000,1250mg, p.o. once daily
- Primary Outcome Measures
Name Time Method Maximum tolerated dose(MTD) 21 days Dose-limiting toxicity(DLT) 21 days
- Secondary Outcome Measures
Name Time Method Pharmacokinetics 21 days Selatinib Ditosilate pharmacokinetic parameters , include AUC, Cmax, Tmax, and t1/2
Pharmacodynamics 7 weeks The response of Salatinib Ditosilate on tumor measured by CT or MRI.
Trial Locations
- Locations (1)
Cancer Institute and Hospital,Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China