Clinical trial NCT03300115: Clinical Trial of the Efficacy and Safety of AC0010 in the Treatment of EGFR T790M Patients With Advanded NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Non-small Cell Lung Cancer
Lead sponsor: Hangzhou ACEA Pharmaceutical Research Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Guangdong Provincial People's Hospital
First posted: 2017-10-03
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ORR(Objective Response Rate)
timeFrame: 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 outcomes:
measure: DoR (Duration of Response)
timeFrame: 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.
measure: PFS (Progression-free survival)
timeFrame: 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.
measure: DCR (Disease control rate)
timeFrame: 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.
measure: OS (Overall survival)
timeFrame: 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.
measure: The lung cancer symptoms and health-related quality of life (HRQoL)
timeFrame: 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.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: Daping Hospital,Research Institute of Surgery Third Military Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Chang chun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Hangzhou First People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital,Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Yilong Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: