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

• ClinicalTrials.gov Identifier: NCT01772732
• Recruitment Status: Unknown
• First Posted: January 21, 2013
• Last Update Posted: April 9, 2015
• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Jiangsu Simcere Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: January 15, 2013
• First Posted Date: January 21, 2013
• Last Update Posted Date: April 9, 2015
• Study Start Date: December 2012
• Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 17, 2013): Maximum tolerated dose (MTD) [ Time Frame: 28 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 17, 2013)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Simotinib Hydrochloride in Patients With Advanced NSCLC
• Official Title: Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Simotinib Hydrochloride in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer
• Intervention: Drug: Simotinib Hydrochloride

Study Arms

Experimental: Simotinib Treatment

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

Intervention: Drug: Simotinib Hydrochloride

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 17, 2013): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2015
• Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01772732
• Other Study ID Numbers: SIM-101-1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Study Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Yuankai Shi, MD; Cancer Institute and Hospital, Chinese Academy of Medical Sciences

• PRS Account: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Verification Date: April 2015