Phase I Dose-escalation Trial of Simmitinib for Patients With Advanced Solid Tumors in Therapeutic Failure
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Dose-limited toxicity (DLT)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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.
Arms & Interventions
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).
Intervention: Simmitinib (Drug)
Outcomes
Primary Outcomes
Dose-limited toxicity (DLT)
Time Frame: 1 year
To identify the dose-limited toxicity (DLT).
Maximum tolerated dose (MTD)
Time Frame: 1 year
To identify the maximum tolerated dose (MTD).
Recommended Phase II Dose (RP2D)
Time Frame: 1 year
To identify the Recommended Phase II Dose (RP2D).
Secondary Outcomes
- Median overall survival (OS)(2 year)
- Time of peak plasma concentration (Tmax)(2 year)
- Median progression free survival (PFS)(2 year)
- Peak Plasma Concentration (Cmax)(2 year)
- Overall response rate (ORR)(2 year)
- Area under the plasma concentration versus time curve (AUC)(2 year)
- Duration of Response (DoR)(2 year)
- Gene status(2 year)