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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

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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: ASP8273 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 23, 2014
Actual Primary Completion Date : January 15, 2016
Actual Study Completion Date : June 14, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Urogastrone

Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase I dose-escalation group
Oral administration
 Drug: ASP8273
Oral administration
Experimental: Phase I EGFR-T790M mutation group
Oral administration
 Drug: ASP8273
Oral administration
Experimental: Phase II group
Oral administration
 Drug: ASP8273
Oral administration


Outcome Measures
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Primary Outcome Measures :
  1. 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)

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Phase I: Plasma concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  6. Phase I: Urine concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  7. 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

  8. 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.

  9. Phase II: Plasma concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  10. Phase II: Urine concentrations of unchanged ASP8273 [ Time Frame: Up to Day 1 of Cycle 3 ]
  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Phase II: Progression-free survival (PFS) [ Time Frame: Up to 18 months ]
  17. Phase II: Overall survival (OS) [ Time Frame: Up to 18 months ]
  18. 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


Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02192697


Locations
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Japan
Site: 4
Fukuoka, Japan
Site: 9
Fukuoka, Japan
Site: 8
Miyagi, Japan
Site: 7
Okayama, Japan
Site: 3
Osaka, Japan
Site: 6
Osaka, Japan
Site: 2
Shizuoka, Japan
Site: 1
Tokyo, Japan
Site: 5
Tokyo, Japan
Korea, Republic of
Site: 10
Seoul, Korea, Republic of
Site: 11
Seoul, Korea, Republic of
Site: 12
Seoul, Korea, Republic of
Taiwan
Site: 13
Taipei, Taiwan
Site: 14
Taipei, Taiwan
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
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Study Director: Medical Director Astellas Pharma Inc
More Information
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Additional Information:

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Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT02192697    
Other Study ID Numbers: 8273-CL-0101
First Posted: July 17, 2014    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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/
Keywords provided by Astellas Pharma Inc:
safety
pharmacokinetics
tolerability
ASP8273
Non-small Cell Lung Cancer
T790M resistance mutation
 NSCLC
Epidermal Growth Factor Receptor mutations
irreversible EGFR inhibitor
antitumor activity
EGFR
Additional relevant MeSH terms:
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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
Naquotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action