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

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ClinicalTrials.gov Identifier: NCT02274337
Recruitment Status : Unknown
Verified November 2016 by Li Zhang, Sun Yat-sen University.
Recruitment status was:  Recruiting
First Posted : October 24, 2014
Last Update Posted : November 23, 2016
Sponsor:
Collaborators:
Acea Bio (Hangzhou) Co., Ltd.
Hangzhou ACEA Pharmaceutical Research Co., Ltd.
Information provided by (Responsible Party):
Li Zhang, Sun Yat-sen University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: AC0010 Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : September 2014
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: AC0010
patients receiving avitinib treatment Qd, at different dose stages
Drug: AC0010
patients take avitinib orally once per day at different dose




Primary Outcome Measures :
  1. Safety, tolerability and ORR of AC0010 [ Time Frame: Adverse events will be collected from baseline until 28 days after the last dose ]
    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 :
  1. 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) ]
    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)

  2. 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) ]
    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)

  3. 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 ]
    Evaluation of tumour response, duration of response, tumour shrinkage, progression free survival and overall survival as assessed by RECIST 1.1

  4. 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02274337


Contacts
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Contact: Yuxiang Ma, MD 86-020-87343894 mayx@sysucc.org.cn

Locations
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China, Guangdong
Sun Yat-Sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Yuxiang Ma, MD    86-020-87343894    mayx@sysucc.org.cn   
Sponsors and Collaborators
Sun Yat-sen University
Acea Bio (Hangzhou) Co., Ltd.
Hangzhou ACEA Pharmaceutical Research Co., Ltd.
Investigators
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Principal Investigator: Li Zhang, professor Sun Yat-sen University

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Responsible Party: Li Zhang, Professor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT02274337     History of Changes
Other Study ID Numbers: AC0010-phaseI
First Posted: October 24, 2014    Key Record Dates
Last Update Posted: November 23, 2016
Last Verified: November 2016

Keywords provided by Li Zhang, Sun Yat-sen University:
Epidermal Growth Factor Receptor
Tyrosine Kinase Inhibitor
T790M mutation

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms