A Phase I Trial of Simmitinib in Advanced Solid Tumors

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

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

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Simmitinib

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wen Xu; Phone Number: 0311-67808817; Email: xuwen@cspc.cn
• Study Contact Backup: Name: Xiaowen Liu; Phone Number: 0311-67808817; Email: liuxiaowen@cspc.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
    • Contact: Wen Xu; Phone Number: 0311-67808817; Email: xuwen@cspc.cn
    • Contact: Xiaowen Liu; Phone Number: 0311-67808817; Email: liuxiaowen@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: SOMCL-15-290

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Collaborators: Shanghai Runshi Pharmaceutical Technology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 14, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 2, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SOMCL-15-290-201901

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No