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

NCT02274337 | Unknown Phase 1 DMC

• 1 other identifier: AC0010-phaseI
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Epidermal Growth Factor Receptor; Tyrosine Kinase Inhibitor; T790M mutation

Outcome Measures

Primary Outcomes (1)

• Safety, tolerability and ORR of AC0010

  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

  Adverse events will be collected from baseline until 28 days after the last dose

Secondary Outcomes (4)

• Plasma concentrations and pharmacokinetic parameters of single dose AC0010

  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 and pharmacokinetic parameters of multiple doses AC0010

  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)

• Efficacy of AC0010

  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

• Food effect on AC0010's bioavailibility

  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)

Study Arms (1)

AC0010

EXPERIMENTAL

patients receiving avitinib treatment Qd, at different dose stages

Drug: AC0010

Interventions

AC0010 DRUG

patients take avitinib orally once per day at different dose

AC0010

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Acea Bio (Hangzhou) Co., Ltd.: collaborator
• Hangzhou ACEA Pharmaceutical Research Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

abivertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Li Zhang, professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuxiang Ma, MD

CONTACT

86-020-87343894; mayx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 19, 2014
• First Posted: October 24, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 23, 2016

Record last verified: 2016-11

Locations

CN (1)