A Phase I Trial of Simmitinib in Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04058587
• Other study ID #: SOMCL-15-290-201901
• Status: Recruiting
• Phase: Phase 1
• Start date: June 8, 2020
• Est. completion date: March 31, 2023

Study information

• Verified date: June 2022
• Source: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Contact: Wen Xu
• Phone: 0311-67808817
• Email: xuwen[@]cspc.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: March 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

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).

Locations

Country	Name	City	State
China	CSPC ZhongQi Pharmaceutical Technology Co., Ltd.	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.	Shanghai Runshi Pharmaceutical Technology Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limited toxicity (DLT)	To identify the dose-limited toxicity (DLT).	1 year
Primary	Maximum tolerated dose (MTD)	To identify the maximum tolerated dose (MTD).	1 year
Primary	Recommended Phase II Dose (RP2D)	To identify the Recommended Phase II Dose (RP2D).	1 year
Secondary	Area under the plasma concentration versus time curve (AUC)	To preliminarily evaluate the AUC in patients with advanced solid tumors.	2 year
Secondary	Peak Plasma Concentration (Cmax)	To preliminarily evaluate Cmax in patients with advanced solid tumors.	2 year
Secondary	Time of peak plasma concentration (Tmax)	To preliminarily evaluate Tmax in patients with advanced solid tumors.	2 year
Secondary	Overall response rate (ORR)	To preliminarily evaluate ORR in patients with advanced solid tumors.	2 year
Secondary	Duration of Response (DoR)	To preliminarily evaluate DoR in patients with advanced solid tumors.	2 year
Secondary	Median progression free survival (PFS)	To preliminarily evaluate PFS in patients with advanced solid tumors.	2 year
Secondary	Median overall survival (OS)	To preliminarily evaluate OS in patients with advanced solid tumors.	2 year
Secondary	Gene status	FGFR1-4, VEGFA, CSF1, CSF1R and other related gene status	2 year