Clinical Trials /

Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Advanced Non Small Cell Lung Cancer

NCT02274337

Description:

AC0010 Maleate Capsules is a new, irreversible, Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor.Aim at local advanced or metastatic non-small cell lung cancer patients with EGFR mutation or T790M drug-resistant mutation. The molecular mechanism: by irreversible combining the EGFR-RTKs ATP binding site of cell, selectively suppress the activities of EGFR tyrosine kinase phosphorylation, block the sigal signal transduction system of EGFR, and close the function of ras/raf/MAPK downstream. at last block the tumor cell growth by EGFR induction, and promotes apoptosis. AC0010 Maleate Capsules has three characters: 1. Irreversible combination with EGFR; 2.Efficient suppress the EGFR mutant tumor cell and has no suppression to EGFR wild-type cell; 3. Efficient suppress the EGFR T790M drug-resistant mutation tumor cell.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Advanced Non Small Cell Lung Cancer
  • Official Title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent

Clinical Trial IDs

  • ORG STUDY ID: AC0010-phaseI
  • NCT ID: NCT02274337

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AC0010AC0010

Purpose

AC0010 Maleate Capsules is a new, irreversible, Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor.Aim at local advanced or metastatic non-small cell lung cancer patients with EGFR mutation or T790M drug-resistant mutation. The molecular mechanism: by irreversible combining the EGFR-RTKs ATP binding site of cell, selectively suppress the activities of EGFR tyrosine kinase phosphorylation, block the sigal signal transduction system of EGFR, and close the function of ras/raf/MAPK downstream. at last block the tumor cell growth by EGFR induction, and promotes apoptosis. AC0010 Maleate Capsules has three characters: 1. Irreversible combination with EGFR; 2.Efficient suppress the EGFR mutant tumor cell and has no suppression to EGFR wild-type cell; 3. Efficient suppress the EGFR T790M drug-resistant mutation tumor cell.

Detailed Description

      This study will treat patients with advanced NSCLC who have already received at least one
      course of specific anti-cancer treatment but the tumor has started to re-grow following that
      treatment. This is the first time that this drug is used or tested in patients, and so it
      will help to understand what type of side effects may occur with the drug treatment, it will
      measure the levels of drug in the body, it will also measure the anti-cancer activity. By
      using these pieces of information together the best dose of this drug to use in further
      clinical trials will be selected.

      This study is a multicenter, open-label, two-stage phase I clinical trial. Trial including
      single-dose and successive-dose tolerance research, single-dose and successive-dose
      pharmacokinetic research, food bioavailability study, exploration of different dosing methods
      and tentative evaluation for clinical efficacy. Stage one is a dose escalation study, using
      the modified Fibonacci methods. 7 dose level are set, respectively are 50mg/d 100mg/d 200mg/d
      350mg/d 550mg/d 850mg/d and 1100mg/d. Three patients are enrolled in each dose level, the
      observed indicator is dose-limited toxicity. No DLT occurred of all 3 patients, the dose
      escalate to next level. 1/3 DLT observed, 3 more patients are enrolled in the level, if no
      DLT is observed, the dose escalated to next level, if DLT occurs again, escalation stops. 2/3
      DLT are observed, escalation stops. A recommend phase II dose level will acquire by this
      method. Stage two is a multicenter, open label, one arm successive dose clinical trial, based
      on the dosing level and method acquired in stage one, for further safety evaluation and
      tentative evaluation of clinical efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
AC0010Experimentalpatients receiving avitinib treatment Qd, at different dose stages
  • AC0010

Eligibility Criteria

        Inclusion Criteria:

          -  Patients of either gender, aged from 18 years older to 70.

          -  Histologically or cytologically confirmed metastatic, or unresectable locally
             advanced, recurrent NSCLC.

          -  At least one measurable disease by CT or MRI, according to RECIST Version 1.1.

          -  Documented evidence of any activating EGFR mutation in the tumor tissue.

          -  Have undergone or are able to undergo a biopsy of either primary or metastatic tumor
             tissue within 28 days of dosing of Avitinib, and have tissue available to send to
             central lab for further genetic profiling especially the status of T790M.

          -  Life expectancy of at least 3 months.

          -  ECOG performance status of 0 to 1.

          -  Adequate hematological and physiological functions of heart, lung, liver, and kidney
             according to definitions given in Appendix D.

          -  Disease progression under at least one treatment with current marketed EGFR TKI
             therapy for at least 30 days (e.g. Erlotinib, or Gefitinib, or Afatinib) with
             intervening treatment after most recent EGFR TKI therapy. The washout period for an
             EGFR TKI (Erlotinib, or Gefitinib) is at a minimum of 7 days. The washout period for
             an irreversible EGFR inhibitor (Afatinib) and chemotherapy is at a minimum of 14 days.

          -  Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1
             or less.

          -  NSCLC patients with asymptomatic brain metastasis or drug-controllable brain
             metastasis.

          -  Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior
             to any study-specific evaluation.

        Exclusion Criteria:

          -  No pathology confirmation

          -  History of interstitial lung disease related to prior EGFR inhibitor therapy.

          -  Symptomatic brain metastases or uncontrollable or unstable brain metastasis.

          -  Positive to HCV or HIV antibody.

          -  Treatment with prohibited medications (e.g., concurrent anticancer therapy including
             other chemotherapy, radiation, hormonal, or immunotherapy) ≤14 days prior to treatment
             with Avitinb.

          -  Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's
             method (QTcF) >450 msec (males) or >470 msec (females).

          -  Family history of long QT syndrome.

          -  Treatment with any Category 1 and 2 drugs (See:https://www.crediblemeds.org/ or
             www.qtdrug.org).

          -  Presence of any serious or unstable concomitant systemic disorder incompatible with
             the clinical study (e.g., substance abuse, uncontrolled psychiatric condition,
             uncontrolled intercurrent illness including active infection, arterial thrombosis, and
             symptomatic pulmonary embolism).

          -  Any other reasons for the investigator to consider the patient should not participate
             in the study.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety, tolerability and ORR of AC0010
Time Frame:Adverse events will be collected from baseline until 28 days after the last dose
Safety Issue:
Description:Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations, RECIST1.1, and NCI CTCAE v4.03

Secondary Outcome Measures

Measure:Plasma concentrations and pharmacokinetic parameters of single dose AC0010
Time Frame:Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1 ,4 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48hours post dose)
Safety Issue:
Description:Plasma concentrations of AC0010 and 4 metabolites and pharmacokinetic parameters following single dose with fast in D1 and fed in D4 (Cmax, tmax, AUC, terminal rate constant, clearance, half life, volume of distribution and mean resistance time)
Measure:Plasma concentrations and pharmacokinetic parameters of multiple doses AC0010
Time Frame:Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8 ,15 and 22. D28- pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hours post dose)
Safety Issue:
Description:Plasma concentrations of AC0010 and 4 metabolites and pharmacokinetic parameters following multiple doses (steady state Cmax, tmax, Cmin AUC, clearance, accumulation ratio and time dependency)
Measure:Efficacy of AC0010
Time Frame:CT or MRI at screening and every 4-8 weeks (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months
Safety Issue:
Description:Evaluation of tumour response, duration of response, tumour shrinkage, progression free survival and overall survival as assessed by RECIST 1.1
Measure:Food effect on AC0010's bioavailibility
Time Frame:Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 4 (pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48hours post dose)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sun Yat-sen University

Trial Keywords

  • Epidermal Growth Factor Receptor
  • Tyrosine Kinase Inhibitor
  • T790M mutation

Last Updated

November 21, 2016