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

• ClinicalTrials.gov Identifier: NCT02448251
• Recruitment Status: Terminated
• First Posted: May 19, 2015
• Last Update Posted: October 29, 2019
• Sponsor: ACEA Therapeutics, Inc.
• Information provided by (Responsible Party): ACEA Therapeutics, Inc.

Study Description

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: AC0010MA	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 2015
• Actual Primary Completion Date: October 2019
• Actual Study Completion Date: October 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: single dose per day (QD); Phase I Arm 1: AC0010MA orally taking once daily, starting from 100 mg per day.	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: 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).	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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010

Stanford University

Palo Alto, California, United States, 94304

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30322

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

France

CEPCM - Hopital Timone

Marseille, France, 13005

Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

START-Madrid-FJD

Madrid, Spain, 28040

START-Madrid-CIOCC

Madrid, Spain, 28050

Sponsors and Collaborators

ACEA Therapeutics, Inc.

Investigators

• 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

More Information

• Responsible Party: ACEA Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02448251
• Other Study ID Numbers: AC00102014-101
• First Posted: May 19, 2015
• Last Update Posted: October 29, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms