Clinical trial NCT01931943: A Phase Ib Study of Selatinib Ditosilate Tablets in Patients With Advanced Breast Cancer
Official title: A Phase Ib Study to Evaluate the Tolerability and Pharmacokinetics of Selatinib Ditosilate Tablets in Patients With Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Breast Cancer
Lead sponsor: Qilu Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-08-30
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 .

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.

Primary outcomes:
measure: Dose-limiting toxicity(DLT)
timeFrame: 21 days
measure: Maximum tolerated dose(MTD)
timeFrame: 21 days
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: 21 days
measure: Pharmacodynamics
timeFrame: 7 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Institute and Hospital,Chinese Academy of Medical Sciences
state: Beijing
Study officials:
References:
citation: Zhang T, Li Q, Chen S, Luo Y, Fan Y, Xu B. Phase I study of QLNC120, a novel EGFR and HER2 kinase inhibitor, in pre-treated patients with HER2-overexpressing advanced breast cancer. Oncotarget. 2017 May 30;8(22):36750-36760. doi: 10.18632/oncotarget.13581.