Non Small Cell Lung CancerPhase 1NCT02448251
Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010MA in Advanced Non Small Cell Lung Cancer
A Phase 1 study testing AC0010MA in people with Non Small Cell Lung Cancer, run by ACEA Therapeutics, Inc. at 8 sites in 3 countries.
Trial summary
AC0010MA 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 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- AC0010MA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 8 sitesin 3 countries
- Study dates
- May 2015to Oct 2019
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is male or female, aged 18 years or older at the time of consent; preferably non-Asian.
- Has histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.
- Has at least one measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI), according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
- Has documented evidence of an activating EGFR mutation in the tumor tissue determined by either sequencing or PCR-based technique (Part 1).
- For Part 1 only: subjects with a positive T790M mutation are preferred, but not required. Confirmation of T790M mutation status will be determined from an archived tumor tissue sample or fresh tumor tissue sample obtained via biopsy if archived tissue is not available. In Part 2, subjects must have a confirmed, positive T790M EGFR mutation (acquired T790M EGFR mutation or "de novo" T790M EGFR mutation).
- Has a life expectancy of at least 3 months.
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- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Has adequate hematological and physiological functions.
- Has documented disease progression while receiving at least 30 days of treatment with a currently approved EGFR tyrosine kinase inhibitor (TKI) (e.g., erlotinib, gefitinib or afatinib) with intervening treatment after most recent EGFR TKI therapy (not required for "de novo" T790M EGFR mutation).
- Signed and dated written informed consent obtained prior to any study-specific evaluation.
Who cannot join
- Has a history of interstitial lung disease related to prior EGFR inhibitor therapy.
- Has an EGFR TKI- related toxicity that has NOT resolved to Grade 1 or less.
- Is test positive for hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV) antibody.
- Has received the prohibited therapy (e.g., concurrent anti-cancer therapy including but not limited to: chemotherapy, radiation, hormonal, or immunotherapy) ≤14 days prior to first planned dose of AC0010MA.
- Received prior treatment with AZD9291 (osimertinib) or CO1686 (rociletinib) and experienced disease progression.
- Is a female subject who is pregnant or breastfeeding.
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- Female subjects (if of child bearing potential) and male subjects (with a partner of child bearing potential) must use medically acceptable methods of birth control before study entry, for the duration of the study, and for at least 6 months after the last intake of study drug.
- Has a 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, or symptomatic pulmonary embolism).
- Has any other reason(s) for the investigator to consider that the subject should not participate in the study.
- Is receiving treatment with medication(s) that are known to be strong inhibitors or inducers of CYP3A4/5.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States4 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
Stanford University
Palo Alto, California, 94304
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
START-Madrid-FJD
Madrid, 28040
START-Madrid-CIOCC
Madrid, 28050
About this study
Official title: A Phase I, Multicenter, Open-Label Safety, Pharmacokinetic and Preliminary Efficacy Study of Wild-type Sparing EGFR Inhibitor, AC0010MA, in Adult Patients With Previously Treated EGFRmut and Acquired T790M Mutation Non-Small Cell Lung Cancer (NSCLC)
AC0010MA 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 signal transduction pathway of EGFR and inhibit the function of ras/raf/MAPK downstream, thus block the tumor cell growth by EGFR induction, and promotes apoptosis. AC0010MA Maleate Capsules has three characters: 1. Irreversible binding to EGFR; 2. Effectively suppresses the tumor cell with EGFR mutant while has no suppression to EGFR wild-type cell; 3. Efficient suppress the tumor cell with EGFR T790M drug-resistant mutation.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- AC0010MA
- 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.
AC0010MADrug
Following Phase I, a protocol amendment will be submitted to the IND to specify the selected dose and dose justification to be used in Phase II.
| Study group | Role | What they receive |
|---|---|---|
| single dose per day (QD) | Experimental | Phase I Arm 1: AC0010MA orally taking once daily, starting from 100 mg per day. Receives: Drug: AC0010MA |
| two doses per day (BID) | Experimental | Phase I Arm 2: AC0010MA orally taking twice daily, starting from 200 mg per day (100 mg BID). Arm 2 will be initiated once the drug plasma t1/2 is 10 hours or below in the first dose cohort (100 mg QD). Receives: Drug: AC0010MA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability, and the maximum tolerated dose (MTD) of AC0010MA determined by incidence of dose limiting toxicity (DLT)
To determine the safety and tolerability and to establish the maximum tolerated dose (MTD) of AC0010MA by incidence of dose limiting toxicity (DLT), defined as Grade 3 or 4 adverse events (AEs) and clinical lab abnormalities occurring within the first 28 days of treatment.
Measured: Within the first 28 days of treatment.
Secondary outcomes (7)
Evaluation of tumor response and duration of response of AC0010MA ((objective response rate, ORR)
To characterize tumor response (objective response rate, ORR) and duration of response of AC0010MA as a criterion for further development of AC0010MA in this patient population.
Measured: within the time frame of every 8 weeks (2 cycles) for up to 3 years
Maximum plasma concentration (Cmax) of AC0010MA
To evaluate pharmacokinetic parameter of AC0010MA
Measured: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Time to Cmax
To evaluate pharmacokinetic parameter of AC0010MA
Measured: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Terminal half-life (t1/2)
To evaluate pharmacokinetic parameter of AC0010MA
Measured: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Area under the plasma concentration-time curve
To evaluate pharmacokinetic parameter of AC0010MA
Measured: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Volume of distribution (V/F)
To evaluate pharmacokinetic parameter of AC0010MA
Measured: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Plasma Concentration (CL/F)
To evaluate pharmacokinetic parameter of AC0010MA
Measured: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2015 (estimated)
- Study startMay 2015
- Primary completionOct 2019
- Study completionOct 2019
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.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- ACEA Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vali A. Papadimitrakopoulou, MD, Study director, MD Anderson Cancer Center, Houston, TX, USASuresh S. Ramalingam, MD, Principal investigator, Emory University School of Medicine, Atlanta, GA, USAHeather Wakelee, MD, Principal investigator, Stanford University, Palo Alto, CA, USAKaren L Reckamp, MD, Principal investigator, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02448251
- Sponsor's protocol ID
- AC00102014-101
- Status last verified
- Oct 2019
- First submitted
- 12 May 2015
- Last updated
- 29 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multicenter, Open-Label Safety, Pharmacokinetic and Preliminary Efficacy Study of Wild-type Sparing EGFR Inhibitor, AC0010MA, in Adult Patients With Previously Treated EGFRmut and Acquired T790M Mutation Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02448251
- Acronym / sponsor ID
- AC00102014-101
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 28 participants (actual)
- Lead sponsor
- ACEA Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2015 (actual)
- Primary completion
- Oct 2019 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 19 May 2015 (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.
AC0010MA 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 signal transduction pathway of EGFR and inhibit the function of ras/raf/MAPK downstream, thus block the tumor cell growth by EGFR induction, and promotes apoptosis. AC0010MA Maleate Capsules has three characters: 1. Irreversible binding to EGFR; 2. Effectively suppresses the tumor cell with EGFR mutant while has no suppression to EGFR wild-type cell; 3. Efficient suppress the tumor cell with EGFR T790M drug-resistant mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| single dose per day (QD) | Experimental | Drug: AC0010MAPhase I Arm 1: AC0010MA orally taking once daily, starting from 100 mg per day. |
| two doses per day (BID) | Experimental | Drug: AC0010MAPhase I Arm 2: AC0010MA orally taking twice daily, starting from 200 mg per day (100 mg BID). Arm 2 will be initiated once the drug plasma t1/2 is 10 hours or below in the first dose cohort (100 mg QD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Is male or female, aged 18 years or older at the time of consent; preferably non-Asian.
- Has histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC.
- Has at least one measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI), according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
- Has documented evidence of an activating EGFR mutation in the tumor tissue determined by either sequencing or PCR-based technique (Part 1).
- For Part 1 only: subjects with a positive T790M mutation are preferred, but not required. Confirmation of T790M mutation status will be determined from an archived tumor tissue sample or fresh tumor tissue sample obtained via biopsy if archived tissue is not available. In Part 2, subjects must have a confirmed, positive T790M EGFR mutation (acquired T790M EGFR mutation or "de novo" T790M EGFR mutation).
Key exclusion criteria (10 listed)
- Has a history of interstitial lung disease related to prior EGFR inhibitor therapy.
- Has an EGFR TKI- related toxicity that has NOT resolved to Grade 1 or less.
- Is test positive for hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV) antibody.
- Has received the prohibited therapy (e.g., concurrent anti-cancer therapy including but not limited to: chemotherapy, radiation, hormonal, or immunotherapy) ≤14 days prior to first planned dose of AC0010MA.
- Received prior treatment with AZD9291 (osimertinib) or CO1686 (rociletinib) and experienced disease progression.
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 |
|---|---|---|
| AC0010MAFollowing Phase I, a protocol amendment will be submitted to the IND to specify the selected dose and dose justification to be used in Phase II. | Drug | single dose per day (QD), two doses per day (BID) |
Primary outcome
Safety and tolerability, and the maximum tolerated dose (MTD) of AC0010MA determined by incidence of dose limiting toxicity (DLT)
Time frame: Within the first 28 days of treatment.
To determine the safety and tolerability and to establish the maximum tolerated dose (MTD) of AC0010MA by incidence of dose limiting toxicity (DLT), defined as Grade 3 or 4 adverse events (AEs) and clinical lab abnormalities occurring within the first 28 days of treatment.
7 secondary outcomes
Evaluation of tumor response and duration of response of AC0010MA ((objective response rate, ORR)
Time frame: within the time frame of every 8 weeks (2 cycles) for up to 3 years
Maximum plasma concentration (Cmax) of AC0010MA
Time frame: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Time to Cmax
Time frame: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Terminal half-life (t1/2)
Time frame: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Area under the plasma concentration-time curve
Time frame: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Volume of distribution (V/F)
Time frame: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Plasma Concentration (CL/F)
Time frame: Blood samples will be collected at pre-treatment, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-treatment on Days 1, 8, and 28 in the first treatment cycle (QD and BID) in Phase I
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2019.
- Individual participant dataSharing planned: No
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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.
Vali A. Papadimitrakopoulou, MD study director
MD Anderson Cancer Center, Houston, TX, USA
Suresh S. Ramalingam, MD principal investigator
Emory University School of Medicine, Atlanta, GA, USA
Heather Wakelee, MD principal investigator
Stanford University, Palo Alto, CA, USA
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AC0010MA in people with Non Small Cell Lung Cancer, run by ACEA Therapeutics, Inc. at 8 sites in 3 countries.
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 10 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: stopped early, as of the sponsor's last update on 29 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Spain, France. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability, and the maximum tolerated dose (MTD) of AC0010MA determined by incidence of dose limiting toxicity (DLT) (time frame: Within the first 28 days of treatment.). 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 29 Oct 2019; AzTrials last refreshed its copy on 7 Nov 2026.