A Phase I Trial of Simmitinib in Advanced Solid Tumors

CSPC Pharmaceutical Group

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Simmitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04058587

SOMCL-15-290-201901

Details and patient eligibility

About

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

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Simmitinib tablet

Experimental group

Description:

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).

Treatment:

Drug: Simmitinib