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

• ClinicalTrials.gov Identifier: NCT02192697
• Recruitment Status: Terminated
• First Posted: July 17, 2014
• Last Update Posted: October 17, 2019
• Sponsor: Astellas Pharma Inc
• Information provided by (Responsible Party): Astellas Pharma Inc

Study Description

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

• 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

Arms and Interventions

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

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

• 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

Locations

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

• Study Director: Medical Director; Astellas Pharma Inc

More Information

Additional Information:

Link to results on the Astellas Clinical Study Results website 

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT02192697
• Other Study ID Numbers: 8273-CL-0101
• First Posted: July 17, 2014
• 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:

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