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An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02192697
Recruitment Status : Terminated (Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.)
First Posted : July 17, 2014
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Tracking Information
First Submitted Date  ICMJE May 28, 2014
First Posted Date  ICMJE July 17, 2014
Last Update Posted Date October 17, 2019
Actual Study Start Date  ICMJE January 23, 2014
Actual Primary Completion Date January 15, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DLTs) [ Time Frame: Up to Day 23 ]
    A DLT is defined as any pre-determined toxicity that is related to study drug per the investigator and which occurs during Cycle 0 and Cycle 1 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE ver 4.0 - JCOG)
  • Phase II: Overall response rate (CR+PR) at Week 24 [ Time Frame: Week 24 ]
    The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2014)
  • Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DTLs) [ Time Frame: Up to 18 months ]
    A DLT is defined as any pre-determined toxicity that is related to study drug per the investigator and which occurs during Cycle 0 and Cycle 1 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE ver 4.0 - JCOG)
  • Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs) [ Time Frame: Up to 18 months ]
    An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product
  • Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests [ Time Frame: Up to 18 months ]
    Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation
  • Phase I: Safety and tolerability of ASP8273 as assessed by vital signs [ Time Frame: Up to 18 months ]
    Vital signs to be measured includes blood pressure, pulse rate and temperature
  • Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG [ Time Frame: Up to 18 months ]
    including the assessment of QT intervals
  • Phase II: Overall response rate (CR+PR) [ Time Frame: On Day 1 of every odd-numbered cycle ]
    The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs) [ Time Frame: Up to 18 months ]
    An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product
  • Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests [ Time Frame: Up to 18 months ]
    Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation
  • Phase I: Safety and tolerability of ASP8273 as assessed by vital signs [ Time Frame: Up to 18 months ]
    Vital signs to be measured includes blood pressure, pulse rate and temperature
  • Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG [ Time Frame: Up to 18 months ]
    including the assessment of QT intervals
  • Phase I: Plasma concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase I: Urine concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase I: Overall response rate (CR+PR) [ Time Frame: Up to 18 months ]
    The overall response rate is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated
  • Phase I: Disease control rate (CR+PR+SD) [ Time Frame: Up to 18 months ]
    The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.
  • Phase II: Plasma concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase II: Urine concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase II: Safety and tolerability of ASP8273 as assessed by adverse events (AEs) [ Time Frame: Up to 18 months ]
    An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product
  • Phase II: Safety and tolerability of ASP8273 as assessed by laboratory tests [ Time Frame: Up to 18 months ]
    Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation
  • Phase II: Safety and tolerability of ASP8273 as assessed by vital signs [ Time Frame: Up to 18 months ]
    Vital signs to be measured includes blood pressure, pulse rate and temperature
  • Phase II: Safety and tolerability of ASP8273 as assessed by 12-lead ECG [ Time Frame: Up to 18 months ]
    including the assessment of QT intervals
  • Phase II: Disease control rate [ Time Frame: Up to 18 months ]
    The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.
  • Phase II: Progression-free survival (PFS) [ Time Frame: Up to 18 months ]
  • Phase II: Overall survival (OS) [ Time Frame: Up to 18 months ]
  • Phase II: Overall response rate (CR+PR) [ Time Frame: Up to 18 months ]
    The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2014)
  • Phase I: Plasma concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase I: Urine concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase I: Overall response rate (CR+PR) [ Time Frame: Up to 18 months ]
    The overall response rate is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated
  • Phase I: Disease control rate (CR+PR+SD) [ Time Frame: Up to 18 months ]
    The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.
  • Phase II: Plasma concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase II: Urine concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  • Phase II: Safety and tolerability of ASP8273 as assessed by adverse events (AEs) [ Time Frame: Up to 18 months ]
    An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product
  • Phase II: Safety and tolerability of ASP8273 as assessed by laboratory tests [ Time Frame: Up to 18 months ]
    Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation
  • Phase II: Safety and tolerability of ASP8273 as assessed by vital signs [ Time Frame: Up to 18 months ]
    Vital signs to be measured includes blood pressure, pulse rate and temperature
  • Phase II: Safety and tolerability of ASP8273 as assessed by 12-lead ECG [ Time Frame: Up to 18 months ]
    including the assessment of QT intervals
  • Phase II: Disease control rate [ Time Frame: Up to 18 months ]
    The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.
  • Phase II: Progression-free survival (PFS) [ Time Frame: Up to 18 months ]
  • Phase II: Overall survival (OS) [ Time Frame: Up to 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations
Official Title  ICMJE An Open-label Study of the Oral Administration of ASP8273 in Patients With Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor (EGFR) Mutations
Brief Summary

Purpose of the study is to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

  • the safety and tolerability of ASP8273.
  • the pharmacokinetics (PK) of ASP8273.
  • the antitumor activity of ASP8273.
Detailed Description

This study consists of Phase I and Phase II.

The objectives of Phase I are to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

  • safety and tolerability of ASP8273.
  • the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ASP8273 based on the dose limiting toxicity (DLT) profile.
  • pharmacokinetics (PK) of ASP8273.
  • antitumor activity of ASP8273.

The objectives of Phase II are to determine the following at the RP2D of ASP8273 in patients with NSCLC harboring EGFR mutation.

  • efficacy of ASP8273
  • safety of ASP8273
  • PK of ASP8273
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE Drug: ASP8273
Oral administration
Study Arms  ICMJE
  • Experimental: Phase I dose-escalation group
    Oral administration
    Intervention: Drug: ASP8273
  • Experimental: Phase I EGFR-T790M mutation group
    Oral administration
    Intervention: Drug: ASP8273
  • Experimental: Phase II group
    Oral administration
    Intervention: Drug: ASP8273
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 15, 2014)
124
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 14, 2017
Actual Primary Completion Date January 15, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of NSCLC.
  • Patients confirmed to have the del ex19, L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study).
  • Life expectancy ≥ 12 weeks based on the investigator's/subinvestigator's judgment.
  • [Phase I]

    • Patients who have previously been treated with EGFR tyrosine-kinase inhibitors (EGFR-TKIs)*
    • Those who are not expected to show a therapeutic response to existing treatments in the investigator's/subinvestigator's opinion.
  • [Phase II]

    • Patients who have been confirmed to have progressive disease (PD) after previous treatment with EGFR-TKIs*; for those who have received 2 or more regimens of previous treatment, the last regimen before enrollment should have included EGFR-TKIs.
    • *Erlotinib, gefitinib, and EGFR-TKIs under clinical investigation (e.g., neratinib, afatinib, dacomitinib)
    • Expression of the EGFR-T790M mutation as confirmed by a tumor biopsy of the primary or metastatic lesions after confirmation of PD following previous treatment with EGFR-TKIs and before enrollment, or by a tumor tissue sample that had been collected and archived after confirmation of PD following previous treatment with EGFR-TKIs.
    • At least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Exclusion Criteria:

  • Persistent clinical evidence of previous antitumor treatment related toxicity ≥ Grade 2 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCI CTCAE v4.0 - JCOG) (except alopecia and skin toxicities considered irrelevant in study enrollment by the investigator/sub-investigator).
  • History of or concurrent interstitial lung disease
  • Received treatment with a reversible EGFR-TKI (erlotinib or gefitinib) within 8 days before the start of the study treatment.
  • Received previous treatment (except reversible EGFR-TKIs) intended to have antitumor effects or treatment with another investigational drug or an investigational device within 14 days before the start of the study treatment.
  • Previously received treatment with EGFR-TKIs (e.g., CO-1686, AZD9291) that can inhibit EGFR with the T790M mutation.
  • It is planned that the subject will undergo a surgical procedure during the course of the study or the subject still has an unhealed wound after previous surgery
  • Symptomatic central nervous system (CNS) lesions.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan,   Korea, Republic of,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02192697
Other Study ID Numbers  ICMJE 8273-CL-0101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
Responsible Party Astellas Pharma Inc
Study Sponsor  ICMJE Astellas Pharma Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Astellas Pharma Inc
PRS Account Astellas Pharma Inc
Verification Date October 2019

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