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

NCT01772732 | Unknown Phase 1

• 1 other identifier: SIM-101-1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Simotinib; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  28 days

Secondary Outcomes (5)

• 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

Study Arms (1)

Simotinib Treatment

EXPERIMENTAL

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

Drug: Simotinib Hydrochloride

Interventions

Simotinib Hydrochloride DRUG

Simotinib Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 31191007 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yuankai Shi, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuankai Shi, MD

CONTACT

86-10-87788268

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2013
• First Posted: January 21, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 9, 2015

Record last verified: 2015-04

Locations

CN (1)