A Phase I Trial of Simmitinib in Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is an open label, multi-center, phase I study of oral Simmitinib in subjects with advanced solid tumors including gastric cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Simmitinib tablet 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
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).
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- Area under the plasma concentration versus time curve (AUC) [2 year]
To preliminarily evaluate the AUC 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.
- 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.
- Median progression free survival (PFS) [2 year]
To preliminarily evaluate PFS 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Voluntary written informed consent of the patient obtained before any study-specific procedure；
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
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Patients with histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to standard therapy or for whom no standard therapy exist;
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Adequate washing period from last anti-tumor therapy;
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Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
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The expected survival time for more than 12 weeks;
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Adequate bone marrow, hepatic, renal, pancreas, and coagulation function, Blood phosphorus and calcium in the normal range.
Exclusion Criteria:
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Prior treatment with selective FGFR inhibitors or multi-target kinase Inhibitors with FGFR as the main target;
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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;
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Active Central Nervous System (CNS) metastases (brain or leptomeningeal metastases, etc.);
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Any other history of malignancy within 3 years;
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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);
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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；
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Subjects with impaired cardiac function or heart disease of clinical significance;
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Pregnant or lactating women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Beijing | China |
Sponsors and Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Shanghai Runshi Pharmaceutical Technology Co., Ltd
Investigators
- Principal Investigator: Yuankai Shi, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SOMCL-15-290-201901