A Phase I Trial of Simmitinib in Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer.

Detailed Description
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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.

Official Title
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Phase I Dose-escalation Trial of Simmitinib for Patients With Advanced Solid Tumors in Therapeutic Failure

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: Simmitinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simmitinib tablet<br>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). | Drug: Simmitinib<br>* 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).<br>* Other names: SOMCL-15-290;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limited toxicity (DLT) | To identify the dose-limited toxicity (DLT). | 1 year | 
| Maximum tolerated dose (MTD) | To identify the maximum tolerated dose (MTD). | 1 year | 
| Recommended Phase II Dose (RP2D) | To identify the Recommended Phase II Dose (RP2D). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | To preliminarily evaluate the AUC in patients with advanced solid tumors. | 2 year | 
| Peak Plasma Concentration (Cmax) | To preliminarily evaluate Cmax in patients with advanced solid tumors. | 2 year | 
| Time of peak plasma concentration (Tmax) | To preliminarily evaluate Tmax in patients with advanced solid tumors. | 2 year | 
| Overall response rate (ORR) | To preliminarily evaluate ORR in patients with advanced solid tumors. | 2 year | 
| Duration of Response (DoR) | To preliminarily evaluate DoR in patients with advanced solid tumors. | 2 year | 
| Median progression free survival (PFS) | To preliminarily evaluate PFS in patients with advanced solid tumors. | 2 year | 
| Median overall survival (OS) | To preliminarily evaluate OS in patients with advanced solid tumors. | 2 year | 
| Gene status | FGFR1-4, VEGFA, CSF1, CSF1R and other related gene status | 2 year |