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

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

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: selatinib ditosilate tablets

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 .

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Institute and Hospital,Chinese Academy of Medical Sciences
      • Contact: Qing Li; Email: cheryliqing@aliyun.com
      • Sub-Investigator: Qing Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: August 25, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 30, 2013

Study Record Updates

• Last Update Posted (Estimate): August 30, 2013
• Last Update Submitted That Met QC Criteria: August 27, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: QLSLTN-102