Clinical trial NCT02192697: An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-07-17
Enrollment: 124
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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.

Primary outcomes:
measure: Phase I: Safety and tolerability of ASP8273 as assessed by Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 23
measure: Phase II: Overall response rate (CR+PR) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Phase I: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)
timeFrame: Up to 18 months
measure: Phase I: Safety and tolerability of ASP8273 as assessed by laboratory tests
timeFrame: Up to 18 months
measure: Phase I: Safety and tolerability of ASP8273 as assessed by vital signs
timeFrame: Up to 18 months
measure: Phase I: Safety and tolerability of ASP8273 as assessed by 12-lead ECG
timeFrame: Up to 18 months
measure: Phase I: Plasma concentrations of unchanged ASP8273
timeFrame: Up to Day 1 of Cycle 3
measure: Phase I: Urine concentrations of unchanged ASP8273
timeFrame: Up to Day 1 of Cycle 3
measure: Phase I: Overall response rate (CR+PR)
timeFrame: Up to 18 months
measure: Phase I: Disease control rate (CR+PR+SD)
timeFrame: Up to 18 months
measure: Phase II: Plasma concentrations of unchanged ASP8273
timeFrame: Up to Day 1 of Cycle 3
measure: Phase II: Urine concentrations of unchanged ASP8273
timeFrame: Up to Day 1 of Cycle 3
measure: Phase II: Safety and tolerability of ASP8273 as assessed by adverse events (AEs)
timeFrame: Up to 18 months
measure: Phase II: Safety and tolerability of ASP8273 as assessed by laboratory tests
timeFrame: Up to 18 months
measure: Phase II: Safety and tolerability of ASP8273 as assessed by vital signs
timeFrame: Up to 18 months
measure: Phase II: Safety and tolerability of ASP8273 as assessed by 12-lead ECG
timeFrame: Up to 18 months
measure: Phase II: Disease control rate
timeFrame: Up to 18 months
measure: Phase II: Progression-free survival (PFS)
timeFrame: Up to 18 months
measure: Phase II: Overall survival (OS)
timeFrame: Up to 18 months
measure: Phase II: Overall response rate (CR+PR)
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Site: 4
city: Fukuoka
country: Japan
facility: Site: 9
city: Miyagi
country: Japan
facility: Site: 8
city: Okayama
country: Japan
facility: Site: 7
city: Osaka
country: Japan
facility: Site: 3
city: Osaka
country: Japan
facility: Site: 6
city: Shizuoka
country: Japan
facility: Site: 2
city: Tokyo
country: Japan
facility: Site: 1
city: Tokyo
country: Japan
facility: Site: 5
city: Seoul
country: Korea, Republic of
facility: Site: 10
city: Seoul
country: Korea, Republic of
facility: Site: 11
city: Seoul
country: Korea, Republic of
facility: Site: 12
city: Taipei
country: Taiwan
facility: Site: 13
city: Taipei
country: Taiwan
facility: Site: 14
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: