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

• Register: ClinicalTrials.gov
• Last refreshed on: 5 December 2016
• Main ID: NCT02274337
• Date of registration: 19/10/2014
• Prospective Registration: No
• Primary sponsor: Sun Yat-sen University
• Public title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Advanced Non Small Cell Lung Cancer
• Scientific 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
• Date of first enrolment: September 2014
• Target sample size: 100
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02274337
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1/Phase 2

Countries of recruitment

China

Contacts

• Name: Yuxiang Ma, MD

• Name: Li Zhang, professor
• Affiliation: Sun Yat-sen University

• Name: Yuxiang Ma, MD

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Non-Small Cell Lung Cancer

Intervention(s)

Drug: AC0010

Primary Outcome(s)

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

Secondary Outcome(s)

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)]

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]

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)]

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)]

Secondary ID(s)

AC0010-phaseI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Hangzhou ACEA Pharmaceutical Research Co.,Ltd.

Acea Bio (Hangzhou) Co., Ltd.