Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Mitogens

Naquotinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Subjects will receive a single oral dose in tablet formulation on Day 1 of period 1 under fasted condition, then subjects will receive a single oral dose of ASP8273 in capsule formulation on Day 1 of period 2 under fasted condition. Each period will be for 5 days

Subjects will receive a single oral dose in capsule formulation on Day 1 of period 1 under fasted condition, then subjects will receive a single oral dose of ASP8273 in tablet formulation on Day 1 of period 2 under fasted condition. Each period will be for 5 days

All subjects will receive ASP8273 capsules in once-daily dosing for 1 cycle (28 days)

naquotinib

Senior Medical

The objective of this study is to evaluate the bioequivalence of a tablet formulation versus a capsule formulation of ASP8273 following a single dose under fasted condition in subjects with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The study will also evaluate the safety and tolerability of a tablet formulation as a single dose and a capsule formulation as a single and multiple dose of ASP8273 in subjects with NSCLC harboring EGFR mutations.

Study and subjects will be divided into two phases: a pharmacokinetic (PK) and a postpharmacokinetic phase. The pharmacokinetic phase will follow a randomized, 2 period, 2 sequence single dose crossover design. Each period will be 5 days in duration. Within the sequence, both an ASP8273 tablet and ASP8273 capsule will be administered under fasted condition. The postpharmacokinetic phase will consist of up to 1 cycle (28 days) of continuous once daily dosing in post PK phase with ASP8273 capsules. Dose modifications are allowed if necessary in post PK phase and they follow a step-wise dose reduction. Subject is able to re-escalate dose level if reaction is stable.

A Study of ASP8273 in Subjects With Non-small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Mutations

A Phase 1, Randomized, 2-period Crossover Study to Assess Bioequivalence of a Tablet Formulation Versus a Capsule Formulation of ASP8273 in Subjects With Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Cmax: Maximum plasma concentration. Pharmacokinetic phase only

AUCinf: Area under the concentration time curve extrapolated to time infinity. Pharmacokinetic phase only

AUClast: Area under the concentration time curve from time zero to the last quantifiable concentration. Pharmacokinetic phase only

AUC72: Area under the concentration time curve truncated at 72 hours. Pharmacokinetic phase only

t1/2: Terminal elimination half-life. Pharmacokinetic phase only

tmax: The time of maximum concentration. Pharmacokinetic phase only

tlast: The time of last observed concentration. Pharmacokinetic phase only

CL/F: Oral clearance. Pharmacokinetic phase only

Vz/F: Apparent volume of distribution. Pharmacokinetic phase only

For both pharmacokinetic and postpharmacokinetic phases

Vital signs include systolic and blood diastolic pressure, temperature and pulse rate. For both pharmacokinetic and postpharmacokinetic phases

Laboratory values include biochemical, hematological, coagulation and urine analysis. For both pharmacokinetic and postpharmacokinetic phases

Routine 12-lead ECGs will be performed after the subject has been in a supine position for at least 5 minutes. For both pharmacokinetic and postpharmacokinetic phases

Astellas Pharma Global Development, Inc.

Amino Acids

Erlotinib Hydrochloride

Gefitinib

Tyrosine Kinase Inhibitors

Tyrosine

Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).

Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).

Participants received ASP8273 300 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day.

naquotinib mesilate

Participants received erlotinib 150 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Erlotinib

Participants received gefitinib 250 mg was taken orally once daily with water, with or without food, at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Medical Monitor

The purpose of the study was to evaluate the progression free survival (PFS), based on independent radiologic review (IRR), of ASP8273 compared to erlotinib or gefitinib in patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations.

This study also assessed Overall survival (OS); Overall response rate (ORR) as assessed by IRR; PFS as assessed by the investigator; Disease control rate (DCR) as assessed by IRR; Duration of Response (DOR) by IRR; Safety of ASP8273; and Quality of Life (QOL) and patient-reported outcome (PRO) parameters.

A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations

An Open-label, Randomized Phase 3 Efficacy Study of ASP8273 vs Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations

Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com

:

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by IRR. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.

All events of death after the first study drug administration were included.

Percentage of participants with OR was defined as the proportion of participants with best overall response as complete response (CR) or partial response (PR) without confirmation based on the RECIST v1.1 as assessed by the blinded IRR. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on RECIST V1.1, as assessed by local investigator. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.

Percentage of participants with disease control was defined as the proportion of participants whose best overall response was rated as CR, PR or stable disease (SD) among all analyzed participants based on RECIST V1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug.

DOR was defined as the time from the date of the first response CR/PR (whichever was first recorded) as assessed by IRR to the date of radiographical progression or date of censoring. If a participant had not progressed, the participant was censored at the date of last radiological assessment or at the date of first CR/PR if no post-baseline radiological assessment was available. Results are based Kaplan-Meier estimate.

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.

ACT-EGFRI-18 is an 18-item Likert-scaled questionnaire, used to assess the effect of EGFR inhibitors on quality of life (QoL). The questionnaire is arranged in three HRQL dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 to 4, and the response categories include "not at all", "a little bit", "somewhat", "quite a bit", and "very much." Negatively worded items (e.g., "My skin bleeds easily "or "My skin condition affects my mood") are reverse-scored, so that participants who experience a higher impact of symptom burden on HRQL receive a lower score (range 0-72).

The EORTC-QLQ-LC13 is a validated module of the EORTC-QLQ-Core 30, which includes module items that evaluate symptoms such as cough, hemoptysis, shortness of breath, sore mouth or tongue, dysphagia, tingling hands or feet, hair loss and pain. The total score for the questionnaire ranges from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

EORTC-QLQ-LC30 is a 30-item cancer-specific questionnaire with multitrait scaling was used to create five functional domain scales: Physical, Role, Emotional, Social and Cognitive; two items evaluate global QoL; in addition, three symptom scales assess Fatigue, Pain and Emesis; and six single items assess other symptoms. The total score ranges from 0 to 100, with a high score for a functional scale representing a high/healthy level of functioning and a high score for a symptom scale or item representing a high level of symptomatology or problems.

The EQ-5D is a generic preference-based measure that indirectly measures the utility for health that generates an index-based summary score based upon societal preference weights. The EQ-5D-5L consists of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale (VAS) for health status. Each item has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The VAS ranges from 0 (worst health status) and 100 (best health status).

ASP8273

Erlotinib or Gefitinib

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

American Indian or Alaska Native

Native Hawaiian or Other Pacific Islander

Other

Missing

Race/Ethnicity, Customized

Investigator Prerandomization Selected TKI at Randomization

ECOG Performance Status is composed of 6 grades: 0 - Fully active, able to carry on all predisease performance without restriction; 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2 - Ambulatory and capable of all self-care but unable to carry out any work activities, Up and about more than 50% of waking hours; 3 - Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 - Completely disabled, Cannot carry on any self-care, Totally confined to bed or chair; 5 - Dead.

ECOG Performance Status at Randomization

EGFR Mutation Status at Randomization

Race (Asian vs Non-Asian) at Randomization

The analysis population for all baseline measures consisted of all participants who were randomized in the study.

Senior Medical Director

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using log-rank test stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025. Hazard ratio based on Cox proportional hazards model. Assuming proportional hazards, HR \< 1 indicated a reduction in hazard rate in favor of ASP8273 treatment group.

The analysis population was the full analysis set (FAS), which consisted of all participants who were randomized.

Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)

The analysis population was the safety analysis set (SAF), which consisted of all participants who took at least one dose of study drug.

Percentage of Deaths

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using stratified Cochran-Mantel-Haenszel (CMH) test, stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025.

Percentage of Participants With Objective Response (OR)

PFS as Assessed by the Investigator

Percentage of Participants With Disease Control

The analysis population was the FAS. Only participants with best overall response as CR or PR (without confirmation) were included in the analysis.

Duration of Response (DOR)

TEAE

Drug-Related TEAE

Serious TEAE

Drug-Related Serious TEAE

TEAE Leading to Death

Drug-Related TEAE Leading to Death

TEAE Leading to Treatment Withdrawal

Drug-Related TEAE Leading to Treatment Withdrawal

TEAE Leading to Dose Reduction

Drug-Related TEAE Leading to Dose Reduction

TEAE Leading to Dose Interruption

Drug-Related TEAE Leading to Dose Interruption

Death

Number of Participants With Adverse Events (AEs)

The analysis population was the SAF, with available data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ASP8273 in Subjects With Non-small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Mutations	NCT03082300	Non-small Cell ... Epidermal Growt...	naquotinib	18 Years -	Astellas Pharma Inc
A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations	NCT02588261	Non-small Cell ...	naquotinib mesi... Erlotinib Gefitinib	18 Years -	Astellas Pharma Inc
A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations	NCT02588261	Non-small Cell ...	naquotinib mesi... Erlotinib Gefitinib	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for naquotinib

Every month we try and update this database with for naquotinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for naquotinib

Every month we try and update this database with for naquotinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for naquotinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.