Clinical Trial of the Efficacy and Safety of AC0010 in the Treatment of EGFR T790M Patients With Advanded NSCLC

Single-arm,Multi-center,Phase II Clinical Trial of the Efficacy and Safety of AC0010 in the Treatment of EGFR T790M Mutation-positive Patients With Advanded NSCLC

The study is a single-arm, multi-center, open-label clinical trial. The study aims to expand the sample size based on the fixed dose recommended by the results of previous dose exploration studies in order to further evaluate the study drug's efficacy and safety.

Study Overview

• Status: Unknown
• Conditions: Metastatic Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: AC0010

Detailed Description

The study is a single-arm, multi-center, open-label clinical trial. The study aims to expand the sample size based on the fixed dose recommended by the results of previous dose exploration studies in order to further evaluate the study drug's efficacy and safety with overall objective tumor response rate (ORR) as the primary efficacy evaluation indicator, and further evaluate subjects' duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and quality of life (QoL). Safety indicators of subjects are further evaluated through adverse events, vital signs and clinical laboratory parameters.

• Study Type: Interventional
• Enrollment (Anticipated): 222
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Junling Li
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Zhefeng Liu
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Daping Hospital,Research Institute of Surgery Third Military Medical University
      • Contact: Yong He
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Cheng Huang
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Yilong Wu
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • Recruiting
      • The People's Hospital of Guangxi Zhuang Autonomous Region
      • Contact: Guosheng Feng
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Conghua Xie
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • TongJi Medical College of HUST
      • Contact: Yuan Chen
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Xiangya Hospital Central South University
      • Contact: Chengping Hu
    • Changsha, Hunan, China, 410000
      • Recruiting
      • The Third Xiangya Hospital of Central South University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Jian'an Huang
    • Yangzhou, Jiangsu, China, 225000
      • Recruiting
      • Northern Jiangsu People's Hospital
      • Contact: Buhai Wang
  • Jilin
    • Chang chun, Jilin, China, 130000
      • Recruiting
      • Jilin Cancer Hospital
    • Changchun, Jilin, China, 130000
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Jiuwei Cui
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Shandong Cancer Hospital
      • Contact: Zhehai Wang
  • Shanxi
    • Xi'an, Shanxi, China, 710000
      • Recruiting
      • Tangdu Hospital
      • Contact: Helong Zhang
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Zongan Liang
      • Principal Investigator: Zongan Liang
      • Principal Investigator: Jiang Zhu
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Recruiting
      • Tianjin cancer hospital
    • Tianjin, Tianjin, China, 300000
      • Recruiting
      • Tianjin Medical University General Hospital
      • Contact: Jun Chen
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Zhejiang Cancer Hospital
      • Principal Investigator: Yiping Zhang
      • Principal Investigator: Yun Fan
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Jianjin Huang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Hangzhou First People's Hospital
      • Contact: Limin Wang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Sir Run Run Shaw Hospital，Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-75 years (including 18 and 75 years old).
2. Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent non-small cell lung cancer which cannot receive radical surgery and radiotherapy.
3. The patient has at least one radio graphically (CT, MRI)measurable lesion according to the RECIST criteria for solid tumor response; long-diameter of tumor scanned by CT&MRI ≥10mm, or short-diameter of metastatic cervical lymph nodes≥15mm. With no radiotherapy and biopsy.
4. Patients without CNS metastases or asymptomatic patients with brain metastases. The number of CNS metastases focus≤2, maximum diameter <10mm.
5. Document prove EGFR mutation before treatment of EGFR TKI, or show clinical benefit after treatment of EGFR TKI (PR, CR evaluation according to RECIST or more than half-year SD duration); tumor tissue proved to be EGFR T790M positive mutation by center lab after last treatment.
6. Patients need to undergo biopsy of primary or metastatic tumor tissue and provide pathological sections to site's central lab; otherwise, the patients need to undergo biopsy of primary or metastatic tumor tissue in the screening period and provide pathological sections to the site's central laboratory.
7. Patients who have previously received first-generation EGFR-TKI (erlotinib, gefitinib, ectectin) treatment and developed resistance and are only allowed to have received one chemotherapy regimen (maintenance treatment with the same drug is allowed; but maintenance treatment with a different drug is not allowed), or are positive for primary T790M mutation but have not received treatment or have only received first-line treatment.
8. The patient must have good organ function, including meeting the laboratory test requirements at screening.
9. Patients must recover to ≤Grade 1 (CTCAE v4.03)toxicity from the previous treatment (patients with any grade of hair loss are allowed to enter the study).
10. ECOG score: 0-1 points. No deterioration in the last 2 weeks.
11. Expected survival time:> 12 weeks.
12. Patients who can cooperate with the observation of adverse events and efficacy.
13. Patients or their legal representatives have signed a written informed consent form.

Exclusion Criteria:

1. Acute hepatitis C, chronic hepatitis C and active hepatitis B (positive HBsAg; HBcAb or HBeAb positive and HBV DNA positive).
2. HIV antibody positive, or other acquired, congenital immunodeficiency disease, or a history of organ transplantation.
3. A past history of interstitial lung disease and radiation pneumonia.
4. Clinically significant abnormalities of resting ECG in rhythm, conduction and morphology, such as complete left bundle branch block, Grade II and above heart block, PR interval> 250 ms, or myocardial infarction within the past 6 months; there are risk factors leading to prolongation of QTc interval or increasing arrhythmias, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or medical history of sudden death at an age of < 40 years among the patient's first-degree relatives, and 12-lead ECG QT interval correction Fridericia method (QTcF interval)> 450 ms for male, >470ms for female.

5. The investigator judges based on safety concerns or clinical study process that the patient had any other condition that is prohibited for participation in the clinical study, such as severe infection/inflammation, intestinal obstruction, inability to swallow medication, social/psychological problems, etc.

   With clinically significant electrolyte abnormalities in laboratory tests;

6. In addition to NSCLC, patients who have been diagnosed with another and/or treatment-requiring malignant disease in recent 5 years (this exclusion criterion does not include the following circumstances: completely resected basal cell and squamous cell skin cancer, inert malignant tumor currently requiring no treatment, and any type of completely resected carcinoma in situ).

   Patients who have used high-dose glucocorticoids or other immunosuppressive agents within 1 month prior to screening.

7. Interval time between previous EGFR TKI treatment and AC0010 <8 days or 5 half-time, subject to the long time; Interval time between major surgery /radiotherapy and AC0010 <4 weeks; Patients who are using any drug known to prolong QT interval or known potent CYP3A4 enzyme inducer or inhibitor within 4 weeks before the first dose.

   Patients who have used high-dose glucocorticoids or other immunosuppressive agents within 1 month prior to screening.

8. Patients who have previously administered third-generation EGFR-TKI drugs (e.g.,AZD9291, Avitinib, CO-1686, HM61713, etc.).
9. Patients who have been registered and received the study treatment or withdrawn from the study cannot be enrolled.
10. Pregnant or lactating women.
11. Women with childbearing potential are defined as all women who are physiologically able to have a pregnancy, unless they are using an efficient contraceptive method during treatment and within 7 days after discontinuation of treatment.
12. Patients who are considered by the investigator as inappropriate to participate in the study.

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: AC0010; Each participant will be given AC0010 300mg bid.

Drug: AC0010; After subjects prove eligible after screening and are enrolled, they are given AC0010 300 mg Bid (the two doses are advised to be administered at an interval of 12 hours), receive evaluation of safety indicators every 3 weeks, efficacy evaluation every 6 weeks until disease progression or intolerable toxicities or withdrawal from the trial. (If the investigator suspects disease progression, CT or MRI may be performed in advance; if the patient does not have disease progression, subsequent efficacy evaluation will proceed still according to the protocol).; Other Names: AC0010MA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(Objective Response Rate)	To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).	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 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DoR (Duration of Response)	To assess the duration of response (DOR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).	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 12 months.
PFS (Progression-free survival)	To assess the progression-free survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).	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 12 months.
DCR (Disease control rate)	To assess the disease control rate (DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).	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 12 months.
OS (Overall survival)	To assess the overall survival (OS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).	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 12 months.
The lung cancer symptoms and health-related quality of life (HRQoL)	To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).	Every 3 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 24 months.

Collaborators and Investigators

• Sponsor: Hangzhou ACEA Pharmaceutical Research Co., Ltd.
• Collaborators: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2017
• Primary Completion (Anticipated): June 17, 2019
• Study Completion (Anticipated): December 17, 2020

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Abivertinib
• Other Study ID Numbers: AC201602AVTN03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No