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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor:
Information provided by (Responsible Party):
Jiangsu Simcere Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01772732
First received: January 15, 2013
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Simotinib Hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Simotinib Hydrochloride in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Jiangsu Simcere Pharmaceutical Co., Ltd.:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The maximum plasma concentration (Cmax) [ Time Frame: d1,d8,d9,d10,d15 ] [ Designated as safety issue: No ]
  • The time to Cmax (tmax) [ Time Frame: d1,d8,d9,d10,d15 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: d1,d8,d9,d10,d15 ] [ Designated as safety issue: No ]
  • Overall Response Rate (ORR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Progression-free Survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: December 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Simotinib Treatment
"3+3" design, ascending multiple doses. Simotinib Hydrochloride: 100mg, 200mg, 300mg, 400mg, 500mg, bid, for 28 days
Drug: Simotinib Hydrochloride

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772732

Contacts
Contact: Yuankai Shi, MD 86-10-87788268

Locations
China
Cancer Institute and Hospital, Chinese Academy of Medical Sciences Recruiting
Beijing, China
Contact: Yuankai Shi, MD    86-10-87788268      
Sponsors and Collaborators
Jiangsu Simcere Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Yuankai Shi, MD Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  More Information

No publications provided

Responsible Party: Jiangsu Simcere Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT01772732     History of Changes
Other Study ID Numbers: SIM-101-1
Study First Received: January 15, 2013
Last Updated: July 31, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Jiangsu Simcere Pharmaceutical Co., Ltd.:
Simotinib
Non-small Cell Lung Cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 28, 2014