ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02448251
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02448251
Recruitment Status : Recruiting
First Posted : May 19, 2015
Last Update Posted : February 20, 2018
Sponsor:
Information provided by (Responsible Party):
ACEA Biosciences, Inc.

May 12, 2015
May 19, 2015
February 20, 2018
May 2015
September 2019   (Final data collection date for 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. ]
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.
  • 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.
  • Plasma concentrations and pharmacokinetic parameters of single dose or multiple doses 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 ]
Complete list of historical versions of study NCT02448251 on ClinicalTrials.gov Archive Site
  • 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 ]
    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.
  • 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 ]
    To evaluate pharmacokinetic parameter of AC0010MA
  • 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 ]
    To evaluate pharmacokinetic parameter of AC0010MA
  • 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 ]
    To evaluate pharmacokinetic parameter of AC0010MA
  • 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 ]
    To evaluate pharmacokinetic parameter of AC0010MA
  • 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 ]
    To evaluate pharmacokinetic parameter of AC0010MA
  • 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 ]
    To evaluate pharmacokinetic parameter of AC0010MA
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 ]

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.

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.

Not Provided
Not Provided
 
Safety, Pharmacokinetic and Preliminary Efficacy Study of AC0010MA in Advanced Non Small Cell Lung Cancer
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Non Small Cell Lung Cancer
Drug: AC0010MA
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.
  • Experimental: single dose per day (QD)
    Phase I Arm 1: AC0010MA orally taking once daily, starting from 100 mg per day.
    Intervention: Drug: AC0010MA
  • Experimental: two doses per day (BID)
    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).
    Intervention: Drug: AC0010MA
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
100
September 2019
September 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Jiayin Zhang, MD 858-724-0928 jiayinz@aceabio.com
France,   Spain,   United States
 
 
NCT02448251
AC00102014-101
No
Not Provided
Plan to Share IPD: Undecided
ACEA Biosciences, Inc.
ACEA Biosciences, Inc.
Not Provided
Study Director: Vali A. Papadimitrakopoulou, MD MD Anderson Cancer Center, Houston, TX, USA
Principal Investigator: Suresh S. Ramalingam, MD Emory University School of Medicine, Atlanta, GA, USA
Principal Investigator: Heather Wakelee, MD Stanford University, Palo Alto, CA, USA
Principal Investigator: Karen L Reckamp, MD City of Hope Comprehensive Cancer Center, Duarte, CA, USA
ACEA Biosciences, Inc.
February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP