Preliminary Evaluation of Safety and Efficacy by [14C] AC0010 Trail and Subsequent AC0010 Treatment

An Open-Label, Non-Randomized, Single-Center Study to Preliminary Evaluation of Safety and Efficacy of Patients Who Participant in [14C] AC0010 Trail and Subsequent Receiving AC0010 Treatment

The purpose of this study is to evaluate safety and efficacy of male Patients With Advanced NSCLC who participant in [14C] AC0010 ADME.

Study Overview

• Status: Completed
• Conditions: Carcinoma，Non-Small-Cell Lung
• Intervention / Treatment: Drug: AC0010

Detailed Description

The purpose of this study is to evaluate safety and efficacy of male Patients With Advanced NSCLC who participant in [14C] AC0010 ADME (absorption, distribution, metabolism and excretion) trial and subsequent receiving AC0010 treatment.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• signed and dated informed consent
• histologically or cytologically confirmed diagnosis of local advanced or recurrent NSCLC
• failed to the treatment of EGFR-TKI and harbored T790M mutation
• male, Age 18~ 65, have a body mass index (BMI)>19 kg/m2
• Eastern Cooperative Oncology Group performance status(ECOG PS):0-1,Life expectancy of more than 3 months

• main organs function is normal, laboratory values as listed below: blood test without blood transfusion within 14 days

  1. Haemoglobin >100 g/L
  2. Absolute neutrophil count ≥2.0x10^9/L or WBC ≥3.5 x10^9/L
  3. Platelet count ≥ 80x10^9/L
  4. Total bilirubin ≤1.5xULN
  5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
  6. Serum creatinine ≤1.5xULN or creatinine clearance ratio ≥60 mL/ min
• Any prior treatment (chemotherapy, radiotherapy or surgery) must be completed over 4 weeks(target therapy over 2 weeks) from the screening; Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03)
• International normalized ratio (INR) ≤ 1.5
• Patients and their partners should be willing to use methods of contraception or total abstinence from start of dosing until 6 months after discontinuing of study treatment
• Patients must withdraw from previous study of [14C] AC0010

Exclusion Criteria:

• Prior treated with AC0010 or allergic to drug or its formulation ingredients
• Patients receiving other anti-tumor therapy
• Impairment of GI disease, renal disorders or liver disease that may significantly alter the absorption and metabolic of AC0010 (e.g., Unable to swallow, liver, kidney or gastrointestinal partial resection, chronic diarrhea and intestinal obstruction)
• HCVAb positive, active hepatitis B (excluding HBV carriers), Hepatitis virus markers positive and receiving anti-virus drugs
• Meningeal metastasis; brain metastasis with whole brain radiotherapy; prior received hormones or mannitol for the brain metastasis
• Previous EGFR-TKI treatment related Interstitial lung disease history
• Known human immunodeficiency virus infection (HIV), other acquired or congenital immunodeficiency disease, or a history of organ transplantation
• Any severe and / or uncontrolled active infections
• Patients receiving concomitant immunosuppressive agents or high-dose corticosteroids
• Any severe and / or uncontrolled medical conditions
• Patients being treated with drugs recognized as being inhibitors or inducers of the liver isoenzyme in the last 4 weeks prior to registration in the current study
• Within 3 days prior to the treatment taking of dragon fruit, pomelo, grapefruit, orange, mango and other fruit may affect drug metabolizing enzymes or juice
• Major surgery, incisional biopsy or traumatic injuries;
• Within 4 weeks prior to the screening patients with bleeding ≥ grade 3, non-healing wound, sever ulcer or bone fracture
• Patients received high dose irradiation treatment or other 14C-labeled drug within 1 year
• Known a history of alcoholism or drug abuse
• Investigator judgment that patient is unsuitable to participate in 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; Oral dose of 300mg bid,the two doses are advised to be administered at an interval of 12 hours; Other Names: AC0010MA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	To assess the overall Objective Response Rate(ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced NSCLC.	RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	To assess the Progression Free Survival(PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced NSCLC.	RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months
Disease control rate	To assess the Disease control rate(DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced NSCLC.	RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months
Number of adverse events (AE) experienced by patients to assess safety	To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced NSCLC.	From date of Signed informed consent forms until 30 days after disease progression, intolerable toxicity or withdrawal from study, approximately up to 18 months)

Collaborators and Investigators

• Sponsor: Hangzhou ACEA Pharmaceutical Research Co., Ltd.
• Investigators: Principal Investigator: Lingxiang Liu, Doctor, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: February 10, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: January 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: AC201606AVTN07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO