A Phase I Trial of Simmitinib in Advanced Solid Tumors
- Registration Number
- NCT04058587
- Lead Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Brief Summary
This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer.
- Detailed Description
This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer \[including gastroesophageal cancer\], cholangiocarcinoma, lung squamous cell carcinoma, urothelial transitional cell carcinoma, and estrogen-receptor-positive breast cancer patients \[ER+\], etc. This phase I study will evaluate the safety, tolerability, pharmacokinetics and the preliminary efficacy of the FGFR/KDR/CSF1R multi-target inhibitor Simmitinib.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
- Voluntary written informed consent of the patient obtained before any study-specific procedure；
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
- Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to standard therapy or for whom no standard therapy exist;
- Adequate washing period from last anti-tumor therapy;
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
- The expected survival time for more than 12 weeks;
- Adequate bone marrow, hepatic, renal, pancreas, and coagulation function, Blood phosphorus and calcium in the normal range.
- Prior treatment with selective FGFR inhibitors or multi-target kinase Inhibitors with FGFR as the main target;
- Unrecovered from any drug-related adverse event to grade ≤ 1 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0 derived from any previous anti-tumor treatment, excluding alopecia, Pigmentation, or other toxicity with little safety risk for subjects;
- Active Central Nervous System (CNS) metastases (brain or leptomeningeal metastases, etc.);
- Any other history of malignancy within 3 years;
- Congenital coagulation abnormalities. Active bleeding or previous history of massive bleeding (>30ml within 3 months), history of hemoptysis (more than 5ml fresh bleeding within 4 weeks);
- Corneal diseases of clinical significance. There is a history of retinal pigment epithelial detachment or evidence of the presence of retinal pigment epithelial detachment. History of age-related macular degeneration or evidence of age-related macular degeneration exists；
- Subjects with impaired cardiac function or heart disease of clinical significance;
- Pregnant or lactating women.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Simmitinib tablet Simmitinib The core trial period includes 4-weeks Screening stage (28d), 7-days single administration stage, 4-weeks multiple administration stage (28d), 3-days blood collection stage of PK after multiple administration. The starting dose was set at 1mg/d on toxicology data. Dosing will continue uninterrupted for 28 days in multiple administration stage. The dose-limiting toxicity (DLT) period assessment will be from the first administration of Simmitinib tablet to the end of the first cycle (35 days).
- Primary Outcome Measures
Name Time Method Dose-limited toxicity (DLT) 1 year To identify the dose-limited toxicity (DLT).
Maximum tolerated dose (MTD) 1 year To identify the maximum tolerated dose (MTD).
Recommended Phase II Dose (RP2D) 1 year To identify the Recommended Phase II Dose (RP2D).
- Secondary Outcome Measures
Name Time Method Median overall survival (OS) 2 year To preliminarily evaluate OS in patients with advanced solid tumors.
Time of peak plasma concentration (Tmax) 2 year To preliminarily evaluate Tmax in patients with advanced solid tumors.
Median progression free survival (PFS) 2 year To preliminarily evaluate PFS in patients with advanced solid tumors.
Peak Plasma Concentration (Cmax) 2 year To preliminarily evaluate Cmax in patients with advanced solid tumors.
Overall response rate (ORR) 2 year To preliminarily evaluate ORR in patients with advanced solid tumors.
Area under the plasma concentration versus time curve (AUC) 2 year To preliminarily evaluate the AUC in patients with advanced solid tumors.
Duration of Response (DoR) 2 year To preliminarily evaluate DoR in patients with advanced solid tumors.
Gene status 2 year FGFR1-4, VEGFA, CSF1, CSF1R and other related gene status
Trial Locations
- Locations (1)
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
🇨🇳Beijing, China