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Report for Clinical Trial NCT02588261

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT02588261 Non-small Cell Lung Cancer (NSCLC)
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: naquotinib mesilate

Description: 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.
Type: Drug
Group Labels: 1

ASP8273

Name: Erlotinib

Description: 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.
Type: Drug
Group Labels: 1

erlotinib or gefitinib

Name: Gefitinib

Description: 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.
Type: Drug
Group Labels: 1

erlotinib or gefitinib


Primary Outcomes

Description: 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.

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

Time: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Secondary Outcomes

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

Measure: Percentage of Deaths

Time: From date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months)

Description: 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.

Measure: Percentage of Participants With Objective Response (OR)

Time: From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Description: 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.

Measure: PFS as Assessed by the Investigator

Time: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Description: 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.

Measure: Percentage of Participants With Disease Control

Time: From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Description: 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.

Measure: Duration of Response (DOR)

Time: From date of first response up to data cut-off date 09 May 2017 (approximately 15 months)

Description: 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.

Measure: Number of Participants With Adverse Events (AEs)

Time: From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 09 May 2017

Description: 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).

Measure: Functional Assessment of Cancer Therapy - EGFR Inhibitors Subscale (FACT-EGFRI-18) Questionnaire

Time: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Description: 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.

Measure: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC-QLQ-LC13)

Time: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Description: 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.

Measure: European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)

Time: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Description: 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).

Measure: EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)

Time: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 L858R

- Neutrophil count > 1,000/mm3 - Platelet count ≥ 7.5 x 104 /mm3 - Hemoglobin > 8.0 g/dL - Serum creatinine ˂ 2.0 x upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 mL/min as calculated by the Cockcroft Gault Method - Total bilirubin ˂1.5 x ULN (except for subjects with documented Gilbert's syndrome) - AST and ALT ˂ 3.0 x ULN or ≤ 5 x ULN if subject has documented liver metastases - Serum sodium level is ≥ 130 mmol/L - Subject has an EGFR activating mutation (exon 19 deletion or exon 21 L858R), with or without T790M mutation, by local or central testing on examination of a NSCLC FFPE specimen (archival or fresh biopsy). --- L858R ---

Subjects harboring both exon 19 deletion and exon 21 L858R mutations are not eligible. --- L858R ---


2 T790M

- Neutrophil count > 1,000/mm3 - Platelet count ≥ 7.5 x 104 /mm3 - Hemoglobin > 8.0 g/dL - Serum creatinine ˂ 2.0 x upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 mL/min as calculated by the Cockcroft Gault Method - Total bilirubin ˂1.5 x ULN (except for subjects with documented Gilbert's syndrome) - AST and ALT ˂ 3.0 x ULN or ≤ 5 x ULN if subject has documented liver metastases - Serum sodium level is ≥ 130 mmol/L - Subject has an EGFR activating mutation (exon 19 deletion or exon 21 L858R), with or without T790M mutation, by local or central testing on examination of a NSCLC FFPE specimen (archival or fresh biopsy). --- L858R --- --- T790M ---



HPO Nodes


HPO: