Clinical trial NCT04058587: A Phase I Trial of Simmitinib in Advanced Solid Tumors
Official title: Phase I Dose-escalation Trial of Simmitinib for Patients With Advanced Solid Tumors in Therapeutic Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Runshi Pharmaceutical Technology Co., Ltd
First posted: 2019-08-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limited toxicity (DLT)
timeFrame: 1 year
measure: Maximum tolerated dose (MTD)
timeFrame: 1 year
measure: Recommended Phase II Dose (RP2D)
timeFrame: 1 year
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 2 year
measure: Peak Plasma Concentration (Cmax)
timeFrame: 2 year
measure: Time of peak plasma concentration (Tmax)
timeFrame: 2 year
measure: Overall response rate (ORR)
timeFrame: 2 year
measure: Duration of Response (DoR)
timeFrame: 2 year
measure: Median progression free survival (PFS)
timeFrame: 2 year
measure: Median overall survival (OS)
timeFrame: 2 year
measure: Gene status
timeFrame: 2 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi
role: PRINCIPAL_INVESTIGATOR
References: