Clinical Trials /

Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010MA in Advanced Non Small Cell Lung Cancer

NCT02448251

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010MA in Advanced Non Small Cell Lung Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: AC00102014-101
  • NCT ID: NCT02448251

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AC0010MAsingle dose per day (QD)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
single dose per day (QD)ExperimentalPhase I Arm 1: AC0010MA orally taking once daily, starting from 100 mg per day.
  • AC0010MA
two doses per day (BID)ExperimentalPhase 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).
  • AC0010MA

Eligibility Criteria

        Inclusion Criteria:

          1. Is male or female, aged 18 years or older at the time of consent; preferably
             non-Asian.

          2. Has histologically or cytologically confirmed metastatic, or unresectable locally
             advanced, recurrent NSCLC.

          3. 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.

          4. Has documented evidence of an activating EGFR mutation in the tumor tissue determined
             by either sequencing or PCR-based technique (Part 1).

          5. 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).

          6. Has a life expectancy of at least 3 months.

          7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          8. Has adequate hematological and physiological functions.

          9. 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).

         10. Signed and dated written informed consent obtained prior to any study-specific
             evaluation.

        Exclusion Criteria:

          1. Has a history of interstitial lung disease related to prior EGFR inhibitor therapy.

          2. Has an EGFR TKI- related toxicity that has NOT resolved to Grade 1 or less.

          3. Is test positive for hepatitis C virus (HCV), hepatitis B virus (HBV) or human
             immunodeficiency virus (HIV) antibody.

          4. 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.

          5. Received prior treatment with AZD9291 (osimertinib) or CO1686 (rociletinib) and
             experienced disease progression.

          6. Is a female subject who is pregnant or breastfeeding.

          7. 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.

          8. 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).

          9. Has any other reason(s) for the investigator to consider that the subject should not
             participate in the study.

         10. Is receiving treatment with medication(s) that are known to be strong inhibitors or
             inducers of CYP3A4/5.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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.
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:To evaluate pharmacokinetic parameter of AC0010MA
Measure: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
Safety Issue:
Description:To evaluate pharmacokinetic parameter of AC0010MA
Measure: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
Safety Issue:
Description:To evaluate pharmacokinetic parameter of AC0010MA
Measure: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
Safety Issue:
Description:To evaluate pharmacokinetic parameter of AC0010MA
Measure: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
Safety Issue:
Description:To evaluate pharmacokinetic parameter of AC0010MA
Measure: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
Safety Issue:
Description:To evaluate pharmacokinetic parameter of AC0010MA

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ACEA Therapeutics, Inc.

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