Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010 in Patients With EGFR T790M Positive NSCLC
- Conditions
- Metastatic Non-small Cell Lung Cancer
- Interventions
- Drug: AC0010
- Registration Number
- NCT02330367
- Lead Sponsor
- Hangzhou ACEA Pharmaceutical Research Co., Ltd.
- Brief Summary
AC0010 is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral AC0010; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral AC0010; to assess the safety and efficacy of AC0010 in previously treated mutant EGFR in NSCLC patients with EGFR T790M mutation.
- Detailed Description
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. AC0010 may provide an effective therapy for a patient population with few alternative treatment options. Pre-clinical data demonstrated that AC0010 inhibits T790M. It is anticipated that AC0010 may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to previous TKIs.
This is a two-part, open-label study of oral AC0010 administered twice-daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.
This study will include 2 parts:
phase 1 : Dose-escalation Period with 28-day cycles; Optional Treatment Extension Period starting on Day 29
phase 2 : Evaluation of activity and safety in patients with the EGFR T790M mutation
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 368
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AC0010 AC0010 Oral AC0010 monotherapy
- Primary Outcome Measures
Name Time Method ORR(Objective Response Rate) Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
- Secondary Outcome Measures
Name Time Method OS (Overall survival) Every 6 weeks from time of first dose until objective disease progression, then every 3 months until death of lost of follow-up, up to approximately 18 months To assess the overall survival (OS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
PFS (Progression-free survival) Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months To assess the progression-free survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Adverse events From screening to 30days after end of treatment, which is assessed through study completion To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
DoR (Duration of Response) Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months To assess the duration of response (DOR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
DCR (Disease control rate) Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months To assess the disease control rate (DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
EORTC QLQ-C30 and LC-13 questionnaire From screening to the end of survival follow-up, which is assessed though study completion To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).
Trial Locations
- Locations (17)
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
Jilin Cancer Hospital
🇨🇳Chang Chun, Jilin, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hanzhou, Zhejiang, China
Shanghai Chest Hospital
🇨🇳Shanghai, Shanghai, China
Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China
307 Hospital of PLA
🇨🇳Beijing, Beijing, China
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Nanjing General Hospital of Nanjing Military Command
🇨🇳Nanjing, Jiangsu, China
West China Hospital,Sichuan University
🇨🇳Chendu, Sichuan, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China