Advanced Solid Tumor
Conditions
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.
Interventions
DRUGSimmitinib
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).
Sponsors
Shanghai Runshi Pharmaceutical Technology Co., Ltd
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 2 year | To preliminarily evaluate ORR in patients with advanced solid tumors. |
| Duration of Response (DoR) | 2 year | To preliminarily evaluate DoR 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. |
| Median overall survival (OS) | 2 year | To preliminarily evaluate OS in patients with advanced solid tumors. |
| Gene status | 2 year | FGFR1-4, VEGFA, CSF1, CSF1R and other related gene status |
| 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. |
| Time of peak plasma concentration (Tmax) | 2 year | To preliminarily evaluate Tmax in patients with advanced solid tumors. |
Countries
China
Contacts
Primary ContactWen Xu
Backup ContactXiaowen Liu
Outcome results
None listed