Non-Small Cell Lung CancerPhase 1/2NCT02274337
Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Advanced Non Small Cell Lung Cancer
A Phase 1/2 study testing AC0010 in people with Non-Small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- AC0010
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Sep 2014to Dec 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060
Yuxiang Ma, MD, 86-020-87343894, mayx@sysucc.org.cn
About this study
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
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.
Read the 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- AC0010
- Keywords
- Epidermal Growth Factor Receptor, Tyrosine Kinase Inhibitor, T790M mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AC0010Drug
patients take avitinib orally once per day at different dose
| Study group | Role | What they receive |
|---|---|---|
| AC0010 | Experimental | patients receiving avitinib treatment Qd, at different dose stages Receives: Drug: AC0010 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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)
Measured: 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
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)
Measured: 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
Evaluation of tumour response, duration of response, tumour shrinkage, progression free survival and overall survival as assessed by RECIST 1.1
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study startSep 2014
- Primary completionJun 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Acea Bio (Hangzhou) Co., Ltd., Hangzhou ACEA Pharmaceutical Research Co., Ltd.
- Responsible party
- Principal investigator, Li Zhang, Sun Yat-sen University
- Investigators
- Li Zhang, professor, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02274337
- Sponsor's protocol ID
- AC0010-phaseI
- Status last verified
- Nov 2016
- First submitted
- 19 Oct 2014
- Last updated
- 23 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02274337
- Acronym / sponsor ID
- AC0010-phaseI
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Epidermal Growth Factor Receptor, Tyrosine Kinase Inhibitor, T790M mutation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Acea Bio (Hangzhou) Co., Ltd., Hangzhou ACEA Pharmaceutical Research Co., Ltd.
- Study start
- Sep 2014
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 24 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AC0010 | Experimental | Drug: AC0010patients receiving avitinib treatment Qd, at different dose stages |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AC0010patients take avitinib orally once per day at different dose | Drug | AC0010 |
Primary outcome
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
4 secondary outcomes
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 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)
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li Zhang, professor principal investigator
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AC0010 in people with Non-Small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yuxiang Ma, MD (86-020-87343894, mayx@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety, tolerability and ORR of AC0010 (time frame: Adverse events will be collected from baseline until 28 days after the last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2016.