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

NCT02192697 | Terminated Phase 1

• 1 other identifier: 8273-CL-0101
• Study Type: interventional
• Target: 124
• Locations: 3 countries
• Sites: 14

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.

Conditions

Non-small Cell Lung Cancer

Keywords

safety; pharmacokinetics; tolerability; ASP8273; Non-small Cell Lung Cancer; T790M resistance mutation; NSCLC; Epidermal Growth Factor Receptor mutations; irreversible EGFR inhibitor; antitumor activity; EGFR

Outcome Measures

Primary Outcomes (2)

• Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DLTs)

  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)

  Up to Day 23

• Phase II: Overall response rate (CR+PR) at 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

  Week 24

Secondary Outcomes (18)

• Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)

  Up to 18 months

• Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests

  Up to 18 months

• Phase I: Safety and tolerability of ASP8273 as assessed by vital signs

  Up to 18 months

• Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG

  Up to 18 months

• Phase I: Plasma concentrations of unchanged ASP8273

  Up to Day 1 of Cycle 3

Study Arms (3)

Phase I dose-escalation group

EXPERIMENTAL

Oral administration

Drug: ASP8273

Phase I EGFR-T790M mutation group

EXPERIMENTAL

Oral administration

Drug: ASP8273

Phase II group

EXPERIMENTAL

Oral administration

Drug: ASP8273

Interventions

ASP8273 DRUG

Oral administration

Phase I EGFR-T790M mutation group; Phase I dose-escalation group; Phase II group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (14)

Site: 4

Fukuoka, Japan

Location

Site: 9

Fukuoka, Japan

Location

Site: 8

Miyagi, Japan

Location

Site: 7

Okayama, Japan

Location

Site: 3

Osaka, Japan

Location

Site: 6

Osaka, Japan

Location

Site: 2

Shizuoka, Japan

Location

Site: 1

Tokyo, Japan

Location

Site: 5

Tokyo, Japan

Location

Site: 10

Seoul, South Korea

Location

Site: 11

Seoul, South Korea

Location

Site: 12

Seoul, South Korea

Location

Site: 13

Taipei, Taiwan

Location

Site: 14

Taipei, Taiwan

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

naquotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: July 17, 2014
• Study Start: January 23, 2014
• Primary Completion: January 15, 2016
• Study Completion: June 14, 2017
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

JP (9); KR (3); TW (2)