Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Simotinib Hydrochloride in Patients With Advanced NSCLC

Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Simotinib Hydrochloride in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

The primary objective is to assess the safety and tolerability of multiple doses of Simotinib Hydrochloride in NSCLC patients. The secondary objective is to determine the pharmacokinetic (PK) profile and explore the preliminary anti-tumor activity.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Simotinib Hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuankai Shi, MD; Phone Number: 86-10-87788268

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • Contact: Yuankai Shi, MD; Phone Number: 86-10-87788268

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically or cytologically confirmed diagnosis of advanced NSCLC, who were previously treated with at least one platinum-based chemotherapy regimen, but had disease relapse;
• Patients have ended their chemotherapy or radiotherapy at least 4 weeks prior to study entry and have recovered from any previous toxicity;
• EGFR mutation positive (such as E19del、L858R、L861Q、G719X, etc.);
• Patients with at least one measurable lesion meeting RECIST;
• ECOG performance status 0-2;
• Life expectancy ≥12 weeks;
• Adequate bone marrow function: ANC ≥1.5 × 109/L, PLT≥80 ×109/L, HB ≥90 g/L;
• Adequate hepatic function: serum bilirubin ≤ 2 × ULN, AST and ALT ≤ 2.5 × ULN, and ≤ 5 × ULN are acceptable if the liver has tumor involvement;
• Adequate renal function: endogenous creatinine clearance rate (CrCl) ≥ 60 mL/min or serum creatinine ≤ 1.5 × ULN;
• Females with childbearing potential must have a negative pregnancy test within 7 days prior to treatment and use an approved contraceptive method during the study;
• Males must be surgically sterile or use an approved contraceptive method during the study.

Exclusion Criteria:

• Patients who were previously treated by EGFR inhibitor or other molecular targeting drugs (micromolecular drugs or monoclonal antibodies) such as Iressa, Tarceva, Sutent, Nexavar, Sprycel, Erbitux, Nimotuzumab, Icotinib, Herceptin, etc.;
• The known hypersensitivity to Simotinib or any of the excipients;
• Concurrent treatment with rifampin, rifabutin, rifapentine, dexamethasone, phenytoin sodium, carbamazepine, phenobarbital, Hypericum perforatum, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin;
• CNS metastasis diagnosed recently which has not received surgery or radiotherapy;
• Evidence of interstitial lung disease;
• Pre-existing idiopathic pulmonary fibrosis as evidenced by CT scan at baseline;
• Any serious or uncontrollable systemic disease (such as unstable respiratory disorders, cardiovascular, hepatic or kidney disorders);
• Any unstable systemic disorders (including active infection, uncontrollable hypertension, unstable angina pectoris, congestive heart failure, liver and kidney disorders or metabolism disease);
• Other malignancies diagnosed within the last 5 years with the exception of completely cured cervical cancer in situ, or basal and squamous cell skin cancer;
• Any remarkable eye disorders, especially severe dry eye syndrome, keratoconjunctivitis sicca, herpes keratitis;
• History of nerve or psychiatric disorders, including epilepsy or dementia.

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: Simotinib Treatment; "3+3" design, ascending multiple doses. Simotinib Hydrochloride: 100mg, 200mg, 300mg, 400mg, 500mg, bid, for 28 days	Drug: Simotinib Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD)	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
The maximum plasma concentration (Cmax)	d1,d8,d9,d10,d15
The time to Cmax (tmax)	d1,d8,d9,d10,d15
Area under the plasma concentration-time curve (AUC)	d1,d8,d9,d10,d15
Overall Response Rate (ORR)	1 year
Progression-free Survival (PFS)	1 year

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Hu XS, Han XH, Yang S, Li N, Wang L, Song YY, Mu H, Shi YK. Safety, tolerability, and pharmacokinetics of simotinib, a novel specific EGFR tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer: results of a phase Ib trial. Cancer Manag Res. 2019 May 13;11:4449-4459. doi: 10.2147/CMAR.S189626. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (Estimate): January 21, 2013

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 7, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Non-small Cell Lung Cancer; Simotinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: SIM-101-1