Clinical trial NCT02588261: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer (NSCLC)
Keywords: erlotinib
EGFR mutation
naquotinib
Non-small cell lung cancer (NSCLC)
ASP8273
gefitinib
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2015-10-27
Enrollment: 530
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Subject agrees not to participate in another interventional study while on treatment.
* Female subject must either:

  * Be of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to Screening, or documented surgically sterile
  * Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 28 days after the final study drug administration; And have a negative serum pregnancy test at Screening; And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control (at least 1 of which must be a highly effective method and one must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration.
* Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.
* Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.
* Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
* Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
* Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Subject has histologically confirmed locally advanced, metastatic or unresectable Stage IIIB/IV adenocarcinoma NSCLC (newly diagnosed or recurrent). Subjects with mixed histology are eligible if adenocarcinoma is the predominant histology.
* Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
* Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally within 7 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.

  * 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). Subjects harboring both exon 19 deletion and exon 21 L858R mutations are not eligible. A tissue sample from the same block used to determine eligibility by local testing should be available to send to the central lab for confirmatory testing. Subjects randomized based on local results indicating presence of EGFR mutation may remain on study if central results are discordant.
* Subject must have at least 1 measureable lesion based on RECIST V1.1. Previously irradiated lesions will not be considered as measurable lesions.

Exclusion Criteria:

* Subject has received intervening anticancer treatment or previous treatment with chemotherapy for metastatic disease other than palliative local radiation to painful bone metastases completed at least 1 week prior to the first dose of study drug. The administration of neoadjuvant or adjuvant chemotherapy is allowed as long as it has finalized ≥ 6 months before the first dose of study drug.
* Subject has received a prior treatment with a therapeutic agent targeting EGFR (e.g., afatinib, dacomitinib, ASP8273, etc).
* Subject has received investigational therapy within 28 days or 5 half-lives prior to the first dose of study drug.
* Subject has received radiotherapy within 1 week prior to the first dose of study drug. If the subject received radiotherapy \> 1 week prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response.
* Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy, does not have brain metastasis related symptoms, is not requiring systemic steroids for at least 2 weeks prior to study drug administration, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 2 weeks prior to study drug administration. Steroid inhaler use or ointment treatment for other concomitant medical disease is permitted.
* Subject has received blood transfusions or hematopoietic factor therapy within 14 days prior to the first dose of study drug.
* Subject has had a major surgical procedure (other than a biopsy) within 14 days prior to the first dose of study drug, or one is planned during the course of the study.
* Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
* Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8273, erlotinib or gefitinib.
* Subject has evidence of an active infection requiring systemic therapy within 14 days prior to the planned first dose of study drug.
* Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension (blood pressure \> 150/100 mmHg) or active bleeding diatheses.
* Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
* Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial fibrillation of any grade.
* Subject currently has Class 3 or 4 New York Heart Association congestive heart failure.
* Subject has history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months prior to the planned first dose of study drug.
* Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
* Subject has concurrent corneal disorder or any ophthalmologic condition which, in the investigator's opinion, makes the subject unsuitable for study participation (i.e., advanced cataracts, glaucoma).
* Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
* Subject has another past or active malignancy which requires treatment. Prior carcinoma in situ or non-melanoma skin cancer after curative resection are permitted.
* Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
* Subject has received potent CYP 3A4 inhibitors within 7 days prior to first dose of study drug or proton pump inhibitors such as omeprazole within 14 days prior to first dose of study drug.

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)
timeFrame: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)
Secondary outcomes:
measure: Percentage of Deaths
timeFrame: From date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months)
measure: Percentage of Participants With Objective Response (OR)
timeFrame: From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)
measure: PFS as Assessed by the Investigator
timeFrame: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)
measure: Percentage of Participants With Disease Control
timeFrame: From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)
measure: Duration of Response (DOR)
timeFrame: From date of first response up to data cut-off date 09 May 2017 (approximately 15 months)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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
measure: Functional Assessment of Cancer Therapy - EGFR Inhibitors Subscale (FACT-EGFRI-18) Questionnaire
timeFrame: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
measure: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC-QLQ-LC13)
timeFrame: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
measure: European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)
timeFrame: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
measure: EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)
timeFrame: Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Site US10029
state: California
city: Fountain Valley
country: United States
facility: Site US10025
state: California
city: La Jolla
country: United States
facility: Site US10036
state: California
city: Loma Linda
country: United States
facility: Site US10051
state: California
city: Los Angeles
country: United States
facility: Site US10033
state: California
city: Oxnard
country: United States
facility: Site US10031
state: California
city: Redondo Beach
country: United States
facility: Site US10052
state: California
city: Santa Monica
country: United States
facility: Site US10003
state: California
city: Whittier
country: United States
facility: Site US10018
state: California
city: Glenwood Springs
country: United States
facility: Site US10047
state: Colorado
city: Aventura
country: United States
facility: Site US10013
state: Florida
city: Saint Petersburg
country: United States
facility: Site US10048
state: Florida
city: Atlanta
country: United States
facility: Site US10050
state: Georgia
city: Baton Rouge
country: United States
facility: Site US10042
state: Louisiana
city: Scarborough
country: United States
facility: Site US10037
state: Maine
city: Boston
country: United States
facility: Site US10034
state: Massachusetts
city: Minneapolis
country: United States
facility: Site US10030
state: Minnesota
city: Rochester
country: United States
facility: Site US10027
state: Minnesota
city: Albuquerque
country: United States
facility: Site US10045
state: New Mexico
city: Mount Kisco
country: United States
facility: Site US10012
state: New York
city: Bethlehem
country: United States
facility: Site US10021
state: Pennsylvania
city: Nashville
country: United States
facility: Site US10009
state: Tennessee
city: Nashville
country: United States
facility: Site US10023
state: Tennessee
city: Lacey
country: United States
facility: Site US10011
state: Washington
city: Milwaukee
country: United States
facility: Site US10046
state: Wisconsin
city: Randwick
country: Australia
facility: Site AU61003
state: New South Wales
city: Woolloongabba
country: Australia
facility: Site AU61007
state: Queensland
city: Adelaide
country: Australia
facility: Site AU61005
state: South Australia
city: East Melbourne
country: Australia
facility: Site AU61008
state: Victoria
city: Fitzroy
country: Australia
facility: Site AU61002
state: Victoria
city: Footscray
country: Australia
facility: Site AU61004
state: Victoria
city: Gent
country: Belgium
facility: Site BE32002
state: West-Vlaanderen
city: Toronto
country: Canada
facility: Site CA15006
state: Ontario
city: Montreal
country: Canada
facility: Site CA15002
state: Quebec
city: Santiago
country: Chile
facility: Site CL56001
state: Región Metropolitana De Santia
city: Vina del Mar
country: Chile
facility: Site CL56002
state: Valparaíso
city: Vina del Mar
country: Chile
facility: Site CL56007
state: Valparaíso
city: Pessac
country: France
facility: Site FR33010
state: Gironde
city: Suresnes
country: France
facility: Site FR33011
state: Hauts-de-Seine
city: Creteil
country: France
facility: Site FR33003
state: Ilej-de-France
city: Tours
country: France
facility: Site FR33004
state: Indre-et-Loire
city: Grenoble
country: France
facility: Site FR33006
state: Isère
city: Saint Priest en Jarez
country: France
facility: Site FR33009
state: Loire
city: Bayonne
country: France
facility: Site FR33012
state: Pyrénées-Atlantiques
city: Pierre Benite
country: France
facility: Site FR33007
state: Rhône
city: Freiburg
country: Germany
facility: Site DE49008
state: Baden-Württemberg
city: Karlsruhe
country: Germany
facility: Site DE49005
state: Baden-Württemberg
city: Gauting
country: Germany
facility: Site DE49003
state: Bayern
city: Wurzburg
country: Germany
facility: Site DE49006
state: Bayern
city: Kassel
country: Germany
facility: Site DE49007
state: Hessen
city: Köln
country: Germany
facility: Site DE49004
state: Nordrhein-Westfalen
city: Szekesfehervar
country: Hungary
facility: Site HU36002
state: Fejér
city: Tatabanya
country: Hungary
facility: Site HU36003
state: Tatabánya
city: Szombathely
country: Hungary
facility: Site HU36006
state: Vas
city: Farkasgyepu
country: Hungary
facility: Site HU36004
state: Veszprém
city: Budapest
country: Hungary
facility: Site HU36007
city: Budapest
country: Hungary
facility: Site HU36001
city: Monza
country: Italy
facility: Site IT39004
state: Lombardia
city: Rozzano
country: Italy
facility: Site IT39009
state: Lombardia
city: Aviano
country: Italy
facility: Site IT39011
state: Pordenone
city: Bergamo
country: Italy
facility: Site IT39003
city: Brescia
country: Italy
facility: Site IT39015
city: Cremona
country: Italy
facility: Site IT39002
city: Lucca
country: Italy
facility: Site IT39013
city: Milano
country: Italy
facility: Site IT39014
city: Piacenza
country: Italy
facility: Site IT39012
city: Roma
country: Italy
facility: Site IT39008
city: Matsuyama
country: Japan
facility: Site JP81018
state: Ehime
city: Hiroshima
country: Japan
facility: Site JP81013
state: Hirosima [Hiroshima]
city: Sapporo
country: Japan
facility: Site JP81014
state: Hokkaidô
city: Osakasayama-shi
country: Japan
facility: Site JP81017
state: Hukuoka [Fukuoka]
city: Kurume
country: Japan
facility: Site JP81008
state: Hukuoka
city: Kobe
country: Japan
facility: Site JP81024
state: Hyogo
city: Kanazawa
country: Japan
facility: Site JP81015
state: Isikawa [Ishikawa]
city: Yokohama
country: Japan
facility: Site JP81010
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP81025
state: Kanagawa
city: Sendai
country: Japan
facility: Site JP81012
state: Miyagi
city: Kurashiki
country: Japan
facility: Site JP81016
state: Okayama
city: Miyakojima-ku
country: Japan
facility: Site JP81005
state: Osaka
city: Osakasayama-shi
country: Japan
facility: Site JP81020
state: Osaka
city: Sunto-gun
country: Japan
facility: Site JP81019
state: Shizuoka
city: Sunto-gun
country: Japan
facility: Site JP81001
state: Sizuoka [Shizuoka]
city: Tokyo
country: Japan
facility: Site JP81004
state: Tôkyô [Tokyo]
city: Niigata
country: Japan
facility: Site JP81022
city: Okayama
country: Japan
facility: Site JP81006
city: Wakayama
country: Japan
facility: Site JP81023
city: Hirakata
country: Japan
facility: Site JP81021
state: Ôsaka [Osaka]
city: Osaka-sayama
country: Japan
facility: Site JP81002
state: Ôsaka [Osaka]
city: Cheongiu
country: Korea, Republic of
facility: Site KR82005
state: Chungcheongbugdo
city: Suwon-si
country: Korea, Republic of
facility: Site KR82004
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Site KR82016
state: Gyeonggido [Kyonggi-do]
city: Bundang
country: Korea, Republic of
facility: Site KR82017
state: Gyeonggido
city: Jinju-si
country: Korea, Republic of
facility: Site KR82009
state: Gyeongsangnamdo
city: Jeonju
country: Korea, Republic of
facility: Site KR82003
state: Jeonrabugdo[Chollabuk-do]
city: Seoul
country: Korea, Republic of
facility: Site KR82002
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82001
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82013
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82007
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82008
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82006
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82015
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Site KR82014
state: Seoul Teugbyeolsi
city: Ulsan
country: Korea, Republic of
facility: Site KR82011
state: Ulsan Gwang'yeogsi
city: Busan Gwang'yeogsi
country: Korea, Republic of
facility: Site KR82010
city: Kuantan Pahang
country: Malaysia
facility: Site MY60001
state: Pahang
city: Georgetown
country: Malaysia
facility: Site MY60002
state: Pulau Pinang
city: Kuching
country: Malaysia
facility: Site MY60004
state: Sarawak
city: Arnhem
country: Netherlands
facility: Site NL31001
state: Gelderland
city: Alkmaar
country: Netherlands
facility: Site NL31006
state: Noord-Holland
city: Cercado De Lima
country: Peru
facility: Site PE51001
state: Arequipa
city: Miraflores
country: Peru
facility: Site PE51008
state: Lima
city: San Isidro
country: Peru
facility: Site PE51004
state: Lima
city: Amadora
country: Portugal
facility: Site PT35101
state: Lisboa
city: Lisbon
country: Portugal
facility: Site PT35104
state: Lisboa
city: Coimbra
country: Portugal
facility: Site PT35103
city: Lisboa
country: Portugal
facility: Site PT35102
city: Floresti
country: Romania
facility: Site RO40004
state: Cluj
city: Craiova
country: Romania
facility: Site RO40001
state: Dolj
city: Craiova
country: Romania
facility: Site RO40010
state: Dolj
city: Ploiesti
country: Romania
facility: Site RO40007
state: Prahova
city: Timisoara
country: Romania
facility: Site RO40008
state: Timis
city: Bucuresti
country: Romania
facility: Site RO40012
city: Sibiu
country: Romania
facility: Site RO40006
city: Arkhangelsk
country: Russian Federation
facility: Site RU70012
state: Arkhangel'skaya Oblast'
city: Ufa
country: Russian Federation
facility: Site RU70017
state: Bashkortostan
city: Magnitogorsk
country: Russian Federation
facility: Site RU70009
state: Chelyabinskaya Oblast'
city: Nalchik
country: Russian Federation
facility: Site RU70016
state: Kabardino-Balkarskaya Respublika
city: Pyatigorsk
country: Russian Federation
facility: Site RU70008
state: Stavropol'skiy Kray
city: Saint Petersburg
country: Russian Federation
facility: Site RU70001
city: Singapore
country: Singapore
facility: Site SG65001
state: Central Singapore
city: Singapore
country: Singapore
facility: Site SG65002
state: Central Singapore
city: Barcelona
country: Spain
facility: Site ES34003
state: Catalunya
city: San Sebastian, Guipuzcoa
country: Spain
facility: Site ES34008
state: Guipúzcoa
city: Malaga
country: Spain
facility: Site ES34010
state: Málaga
city: Madrid
country: Spain
facility: Site ES34006
city: Madrid
country: Spain
facility: Site ES34016
city: Ourense
country: Spain
facility: Site ES34004
city: Sevilla
country: Spain
facility: Site ES34005
city: Valencia
country: Spain
facility: Site ES34015
city: Valencia
country: Spain
facility: Site ES34017
city: Valencia
country: Spain
facility: Site ES34002
city: Taichung City
country: Taiwan
facility: Site TW88605
state: Taichung
city: Taoyuan Hsien
country: Taiwan
facility: Site TW88607
state: Taoyuan
city: Kaohsiung
country: Taiwan
facility: Site TW88606
city: Taichung
country: Taiwan
facility: Site TW88603
city: Tainan
country: Taiwan
facility: Site TW88601
city: Tainan
country: Taiwan
facility: Site TW88604
city: Taipei
country: Taiwan
facility: Site TW88608
city: Taipei
country: Taiwan
facility: Site TW88609
city: Taipei
country: Taiwan
facility: Site TW88611
city: Chom Thong
country: Thailand
facility: Site TH66011
state: Chiang Mai
city: Bangkok
country: Thailand
facility: Site TH66001
state: Krung Thep Maha Nakhon [Bangkok]
city: Bangkok
country: Thailand
facility: Site TH66012
state: Krung Thep Maha Nakhon [Bangkok]
city: Chiang Rai
country: Thailand
facility: Site TH66002
city: Khon Kaen
country: Thailand
facility: Site TH66004
city: Songkla
country: Thailand
facility: Site TH66006
city: Chernivtsi
country: Ukraine
facility: Site UA38006
state: Chernivets'ka Oblast'
city: Dnipropetrovsk
country: Ukraine
facility: Site UA38001
state: Dnipropetrovs'ka Oblast'
city: Kryvyi Rih
country: Ukraine
facility: Site UA38005
state: Dnipropetrovs'ka Oblast'
city: Ivano-Frankivsk
country: Ukraine
facility: Site UA38008
state: Ivano-Frankivs'ka Oblast'
city: Lviv
country: Ukraine
facility: Site UA38004
state: L'vivs'ka Oblast'
city: Lutsk
country: Ukraine
facility: Site UA38007
state: Volyns'ka Oblast'
city: Uzhgorod
country: Ukraine
facility: Site UA38009
state: Zakarpats'ka Oblast'
city: Uzhgorod
country: Ukraine
facility: Site UA38003
state: Zakarpats'ka Oblast'
city: Middlesex
country: United Kingdom
facility: Site GB44002
state: Hertfordshire
city: Liverpool
country: United Kingdom
facility: Site GB44001
state: Wirral
city: Sheffield
country: United Kingdom
facility: Site GB44003
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Kelly RJ, Shepherd FA, Krivoshik A, Jie F, Horn L. A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer. Ann Oncol. 2019 Jul 1;30(7):1127-1133. doi: 10.1093/annonc/mdz128.