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Metastatic Non-small Cell Lung CancerPhase 1/2NCT02330367

Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010 in Patients With EGFR T790M Positive NSCLC

A Phase 1/2 study testing AC0010 in people with Metastatic Non-small Cell Lung Cancer, run by Hangzhou ACEA Pharmaceutical Research Co., Ltd. at 17 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

AC0010 is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic 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
368 participants
Where
17 sitesChina
Study dates
Jan 2015to Mar 2023
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 75 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 75.
  • 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.
  • Failed to the treatment of EGFRTKI with definite state of T790M, or harbored T790M mutation without the treatment of EGFRTKI.
  • Offer biopsy sample to central lab if failed or without the treatment of EGFRTKI.
  • Adequate hematological and physiological functions of heart, lung, liver, and kidney according to definitions given in Appendix D.
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  • Any prior treatment (including chemotherapy, radiotherapy, biotherapy and other clinical medicine) must be completed over 28 days or 5 half-lives from the screening.
  • ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 1.
  • NSCLC patients with asymptomatic brain metastasis or drug-controllable brain metastasis.
  • Life expectancy of at least 3 months.
  • Patients should cooperate with investigator to observe adverse events and efficacy.
  • Without other anticancer therapy.
  • Women without pregnancy or breastfeeding.
  • Adequate function of blood coagulation (INR≤1.5)
  • Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.
  • Patients of either gender, aged from 18 years older to 75.
  • 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.
  • Failed to the treatment of EGFR-TKI and harbored T790M mutation.
  • Offer biopsy sample to central lab if failed or without the treatment of EGFRTKI.
  • Patients failed the treatment of EGFR-TKI should be treated with only one kind of medicine. Patients with arbored T790M mutation should be treated with only one kind of medicine or never be treated.
  • Comply with the results of laboratory testing.
  • ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 1 and no deterioration in 2 weeks.
  • Life expectancy of more than 12 weeks.
  • Patients should cooperate with investigator to observe adverse events and efficacy.
  • Women without pregnancy.
  • Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.

Who cannot join

  • No pathology confirmation.
  • HCV positive, active hepatitis B.
  • History of interstitial lung disease related to prior EGFR inhibitor therapy.
  • Positive to HIV antibody or other immunodeficiency disease or organ transplantation.
  • Residue toxicity related to prior therapies > grade 1.
  • BUN or Cr > 1.5 × upper limits of normal.
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  • ALT or AST > 2.5 × upper limits of normal, total bilirubin> 1.5 × upper limits of normal.
  • Fever (temperature>38℃ or any uncontrolled active infections.
  • Patients received high-dose glucocorticoid or any other immunosuppression within 1 month.
  • Any severe or uncontrolled disease, such as mental, neurologic, cardiovascular, respiratory diseases.
  • Patients with symptomatic and untreated brain metastasis.
  • Patients with organic heart disease, cardiac insufficiency, >2 degree heart block, experienced myocardial infarction in 6 months. Abnormal PR, QT, QRS interval (defined as: 12 lead electrocardiogram QT interval correlated to Bazetts (QTcB)>450ms (male) or >470ms (female), PR>240ms, QRS>110ms).
  • Patients receiving medication known to prolong QT interval.
  • Past history of major surgery in 14 days prior to enrollment.
  • Pregnant or lactating women.
  • Any other reasons for the investigator to consider the patient should not participate in the study.
  • Acute and chronic hepatitis C, active hepatitis B (including positive HBsAg and/or HBeAg; HBcAb and/or positive HBeAb and positive HBV DNA), hepatitis E Virus IgM antibody positive.
  • History of interstitial lung disease related to prior EGFR inhibitor therapy.
  • Positive to HIV antibody or other immunodeficiency disease or organ transplantation.
  • Fever (temperature>38℃ or any uncontrolled active infections.
  • Patients received high-dose glucocorticoid or any other immunosuppression within 1 month.
  • Any severe or uncontrolled disease, such as mental, neurologic, cardiovascular, respiratory diseases.
  • ECG showed abnormal rhythm, conduction and form, such as complete left bundle branch block, >2 degree heart block, PR interval >250ms, experienced myocardial infarction in 6 months. Risks leading to prolonged QT interval or arrhythmia, such as heart failure, hypokalemia, congenital long QT, long QT family history or sudden death under 40 years old in first degree relatives (12 lead electrocardiogram QT interval correlated to Bazetts (QTcB) > 450ms.
  • Prior history of malignancies other than NSCLC (except cured malignancy such as removed basal-cell carcinoma and carcinoma in situ) within 5 years.
  • Patients with CNS metastasis (except asymptomatic CNS metastasis with stable radiography in 4 weeks and no long-term use of corticosteroid. CNS metastasis focuses ≤2, maximum diameter of focus <10mm)
  • Radiation field covered more than 30% bone marrow within 4 weeks of enrollment.
  • Lab test of 1ml plasma prove treatment of AZD9291.
  • Patients already received treatment of this research or quite the treatment of this research. Patients treated with 3rd generation of EGFR-TKI (AZD9291, AC0010, BPI-15086, CO-1686, HM61713).
  • Past history of major surgery in 14 days prior to enrollment.
  • Pregnant or lactating women.
  • Patients with uncontrolled pleural effusion and/or pericardial effusion.
  • Any other reasons for the investigator to consider the patient should not participate in the study

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

China17 sites

  • 307 Hospital of PLA

    Beijing, Beijing Municipality, 100000

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100000

  • Cancer Hospital Chinese Academy of Medical Sciences

    Beijing, Beijing Municipality, 100000

  • Chinese PLA General Hospital

    Beijing, Beijing Municipality, 100000

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100000

  • Jilin Cancer Hospital

    Changchun, Jilin, 130000

  • Hunan Cancer Hospital

    Changsha, Hunan, 410000

  • West China Hospital,Sichuan University

    Chengdu, Sichuan, 610000

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350000

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510000

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong

  • The First Affiliated Hospital, Zhejiang University

    Hangzhou, Zhejiang, 310000

  • The Second Affiliated Hospital of Zhejiang University School of Medicine

    Hanzhou, Zhejiang, 310000

  • Jiangsu Cancer Hospital

    Nanjing, Jiangsu, 210000

  • Jiangsu Province Hospital

    Nanjing, Jiangsu, 210000

  • Nanjing General Hospital of Nanjing Military Command

    Nanjing, Jiangsu, 210000

  • Shanghai Chest Hospital

    Shanghai, Shanghai Municipality, 200000

Other trials in China

About this study

Official title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Patients With EGFR T790M Positive Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With EGFR TKIs

AC0010 is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral AC0010; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral AC0010; to assess the safety and efficacy of AC0010 in previously treated mutant EGFR in NSCLC patients with EGFR T790M mutation.

Read the detailed description

Lung cancer remains the most common cancer worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. AC0010 may provide an effective therapy for a patient population with few alternative treatment options. Pre-clinical data demonstrated that AC0010 inhibits T790M. It is anticipated that AC0010 may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to previous TKIs.

This is a two-part, open-label study of oral AC0010 administered twice-daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.

This study will include 2 parts:

phase 1 : Dose-escalation Period with 28-day cycles; Optional Treatment Extension Period starting on Day 29

phase 2 : Evaluation of activity and safety in patients with the EGFR T790M mutation

Being tested
AC0010
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

    Also called AC0010MA

    Phase 1: AC0010 will be administered in escalating dosages in a period of 28-day cycles.

    Phase 2: AC0010 will be administered twice-daily at RP2D.

Study groups in NCT02330367
Study groupRoleWhat they receive
AC0010ExperimentalOral AC0010 monotherapy
Receives: Drug: AC0010

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ORR(Objective Response Rate)

    To assess the overall objective response rate (ORR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months

Secondary outcomes (6)

  1. DoR (Duration of Response)

    To assess the duration of response (DOR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months

  2. PFS (Progression-free survival)

    To assess the progression-free survival (PFS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months

  3. DCR (Disease control rate)

    To assess the disease control rate (DCR) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months

  4. OS (Overall survival)

    To assess the overall survival (OS) of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: Every 6 weeks from time of first dose until objective disease progression, then every 3 months until death of lost of follow-up, up to approximately 18 months

  5. EORTC QLQ-C30 and LC-13 questionnaire

    To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: From screening to the end of survival follow-up, which is assessed though study completion

  6. Adverse events

    To assess the safety of AC0010 in EGFR T790M mutation-positive patients with advanced non-small cell lung cancer (NSCLC).

    Measured: From screening to 30days after end of treatment, which is assessed through study completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jan 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionDec 2022 (estimated)
  4. Study completionMar 2023 (estimated)

Resources

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
368 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02330367
Sponsor's protocol ID
AC201410AVTN02.
Status last verified
Sep 2021
First submitted
31 Dec 2014
Last updated
10 Sep 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Zhang YC, Chen ZH, Zhang XC, Xu CR, Yan HH, Xie Z, Chuai SK, Ye JY, Han-Zhang H, Zhang Z, Bai XY, Su J, Gan B, Yang JJ, Li WF, Tang W, Luo FR, Xu X, Wu YL, Zhou Q. Analysis of resistance mechanisms to abivertinib, a third-generation EGFR tyrosine kinase inhibitor, in patients with EGFR T790M-positive non-small cell lung cancer from a phase I trial. EBioMedicine. 2019 May;43:180-187. doi: 10.1016/j.ebiom.2019.04.030. Epub 2019 Apr 23.

    PubMed 31027916

  • Wang H, Zhang L, Hu P, Zheng X, Si X, Zhang X, Wang M. Penetration of the blood-brain barrier by avitinib and its control of intra/extra-cranial disease in non-small cell lung cancer harboring the T790M mutation. Lung Cancer. 2018 Aug;122:1-6. doi: 10.1016/j.lungcan.2018.05.010. Epub 2018 May 21.

    PubMed 30032814

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AC0010 in people with Metastatic Non-small Cell Lung Cancer, run by Hangzhou ACEA Pharmaceutical Research Co., Ltd. at 17 sites 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 27 inclusion and 32 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 10 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites 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?

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?

ORR(Objective Response Rate) (time frame: Every 6 weeks from time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02330367, which also lists 2 linked publications.

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 10 Sep 2021.

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