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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

— SOLAR  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02588261
• Other study ID #: 8273-CL-0302
• Secondary ID: 2015-002894-39
• Status: Terminated
• Phase: Phase 3
• Start date: February 11, 2016
• Est. completion date: December 21, 2017

Study information

• Verified date: January 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 530
• Est. completion date: December 21, 2017
• Est. primary completion date: December 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• naquotinib mesilate
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.
• Erlotinib
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.
• Gefitinib
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.

Locations

Country	Name	City	State
Australia	Site AU61005	Adelaide	South Australia
Australia	Site AU61008	East Melbourne	Victoria
Australia	Site AU61002	Fitzroy	Victoria
Australia	Site AU61004	Footscray	Victoria
Australia	Site AU61003	Randwick	New South Wales
Australia	Site AU61007	Woolloongabba	Queensland
Belgium	Site BE32002	Gent	West-Vlaanderen
Canada	Site CA15002	Montreal	Quebec
Canada	Site CA15006	Toronto	Ontario
Chile	Site CL56001	Santiago	Región Metropolitana De Santia
Chile	Site CL56002	Vina del Mar	Valparaíso
Chile	Site CL56007	Vina del Mar	Valparaíso
France	Site FR33012	Bayonne	Pyrénées-Atlantiques
France	Site FR33003	Creteil	Ilej-de-France
France	Site FR33006	Grenoble	Isère
France	Site FR33010	Pessac	Gironde
France	Site FR33007	Pierre Benite	Rhône
France	Site FR33009	Saint Priest en Jarez	Loire
France	Site FR33011	Suresnes	Hauts-de-Seine
France	Site FR33004	Tours	Indre-et-Loire
Germany	Site DE49008	Freiburg	Baden-Württemberg
Germany	Site DE49003	Gauting	Bayern
Germany	Site DE49005	Karlsruhe	Baden-Württemberg
Germany	Site DE49007	Kassel	Hessen
Germany	Site DE49004	Köln	Nordrhein-Westfalen
Germany	Site DE49006	Wurzburg	Bayern
Hungary	Site HU36001	Budapest
Hungary	Site HU36007	Budapest
Hungary	Site HU36004	Farkasgyepu	Veszprém
Hungary	Site HU36002	Szekesfehervar	Fejér
Hungary	Site HU36006	Szombathely	Vas
Hungary	Site HU36003	Tatabanya	Tatabánya
Italy	Site IT39011	Aviano	Pordenone
Italy	Site IT39003	Bergamo
Italy	Site IT39015	Brescia
Italy	Site IT39002	Cremona
Italy	Site IT39013	Lucca
Italy	Site IT39014	Milano
Italy	Site IT39004	Monza	Lombardia
Italy	Site IT39012	Piacenza
Italy	Site IT39008	Roma
Italy	Site IT39009	Rozzano	Lombardia
Japan	Site JP81021	Hirakata	Ôsaka [Osaka]
Japan	Site JP81013	Hiroshima	Hirosima [Hiroshima]
Japan	Site JP81015	Kanazawa	Isikawa [Ishikawa]
Japan	Site JP81024	Kobe	Hyogo
Japan	Site JP81016	Kurashiki	Okayama
Japan	Site JP81008	Kurume	Hukuoka
Japan	Site JP81018	Matsuyama	Ehime
Japan	Site JP81005	Miyakojima-ku	Osaka
Japan	Site JP81022	Niigata
Japan	Site JP81006	Okayama
Japan	Site JP81002	Osaka-sayama	Ôsaka [Osaka]
Japan	Site JP81017	Osakasayama-shi	Hukuoka [Fukuoka]
Japan	Site JP81020	Osakasayama-shi	Osaka
Japan	Site JP81014	Sapporo	Hokkaidô
Japan	Site JP81012	Sendai	Miyagi
Japan	Site JP81001	Sunto-gun	Sizuoka [Shizuoka]
Japan	Site JP81019	Sunto-gun	Shizuoka
Japan	Site JP81004	Tokyo	Tôkyô [Tokyo]
Japan	Site JP81023	Wakayama
Japan	Site JP81010	Yokohama	Kanagawa
Japan	Site JP81025	Yokohama	Kanagawa
Korea, Republic of	Site KR82017	Bundang	Gyeonggido
Korea, Republic of	Site KR82010	Busan Gwang'yeogsi
Korea, Republic of	Site KR82005	Cheongiu	Chungcheongbugdo
Korea, Republic of	Site KR82003	Jeonju	Jeonrabugdo[Chollabuk-do]
Korea, Republic of	Site KR82009	Jinju-si	Gyeongsangnamdo
Korea, Republic of	Site KR82001	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82002	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82006	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82007	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82008	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82013	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82014	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Site KR82015	Seoul	Seoul Teugbyeolsi [Seoul-T'ukp]
Korea, Republic of	Site KR82004	Suwon-si	Gyeonggi-do
Korea, Republic of	Site KR82016	Suwon-si	Gyeonggido [Kyonggi-do]
Korea, Republic of	Site KR82011	Ulsan	Ulsan Gwang'yeogsi
Malaysia	Site MY60002	Georgetown	Pulau Pinang
Malaysia	Site MY60001	Kuantan Pahang	Pahang
Malaysia	Site MY60004	Kuching	Sarawak
Netherlands	Site NL31006	Alkmaar	Noord-Holland
Netherlands	Site NL31001	Arnhem	Gelderland
Peru	Site PE51001	Cercado De Lima	Arequipa
Peru	Site PE51008	Miraflores	Lima
Peru	Site PE51004	San Isidro	Lima
Portugal	Site PT35101	Amadora	Lisboa
Portugal	Site PT35103	Coimbra
Portugal	Site PT35102	Lisboa
Portugal	Site PT35104	Lisbon	Lisboa
Romania	Site RO40012	Bucuresti
Romania	Site RO40001	Craiova	Dolj
Romania	Site RO40010	Craiova	Dolj
Romania	Site RO40004	Floresti	Cluj
Romania	Site RO40007	Ploiesti	Prahova
Romania	Site RO40006	Sibiu
Romania	Site RO40008	Timisoara	Timis
Russian Federation	Site RU70012	Arkhangelsk	Arkhangel'skaya Oblast'
Russian Federation	Site RU70009	Magnitogorsk	Chelyabinskaya Oblast'
Russian Federation	Site RU70016	Nalchik	Kabardino-Balkarskaya Respublika
Russian Federation	Site RU70008	Pyatigorsk	Stavropol'skiy Kray
Russian Federation	Site RU70001	Saint Petersburg
Russian Federation	Site RU70017	Ufa	Bashkortostan
Singapore	Site SG65001	Singapore	Central Singapore
Singapore	Site SG65002	Singapore	Central Singapore
Spain	Site ES34003	Barcelona	Catalunya
Spain	Site ES34006	Madrid
Spain	Site ES34016	Madrid
Spain	Site ES34010	Malaga	Málaga
Spain	Site ES34004	Ourense
Spain	Site ES34008	San Sebastian, Guipuzcoa	Guipúzcoa
Spain	Site ES34005	Sevilla
Spain	Site ES34002	Valencia
Spain	Site ES34015	Valencia
Spain	Site ES34017	Valencia
Taiwan	Site TW88606	Kaohsiung
Taiwan	Site TW88603	Taichung
Taiwan	Site TW88605	Taichung City	Taichung
Taiwan	Site TW88601	Tainan
Taiwan	Site TW88604	Tainan
Taiwan	Site TW88608	Taipei
Taiwan	Site TW88609	Taipei
Taiwan	Site TW88611	Taipei
Taiwan	Site TW88607	Taoyuan Hsien	Taoyuan
Thailand	Site TH66001	Bangkok	Krung Thep Maha Nakhon [Bangkok]
Thailand	Site TH66012	Bangkok	Krung Thep Maha Nakhon [Bangkok]
Thailand	Site TH66002	Chiang Rai
Thailand	Site TH66011	Chom Thong	Chiang Mai
Thailand	Site TH66004	Khon Kaen
Thailand	Site TH66006	Songkla
Ukraine	Site UA38006	Chernivtsi	Chernivets'ka Oblast'
Ukraine	Site UA38001	Dnipropetrovsk	Dnipropetrovs'ka Oblast'
Ukraine	Site UA38008	Ivano-Frankivsk	Ivano-Frankivs'ka Oblast'
Ukraine	Site UA38005	Kryvyi Rih	Dnipropetrovs'ka Oblast'
Ukraine	Site UA38007	Lutsk	Volyns'ka Oblast'
Ukraine	Site UA38004	Lviv	L'vivs'ka Oblast'
Ukraine	Site UA38003	Uzhgorod	Zakarpats'ka Oblast'
Ukraine	Site UA38009	Uzhgorod	Zakarpats'ka Oblast'
United Kingdom	Site GB44001	Liverpool	Wirral
United Kingdom	Site GB44002	Middlesex	Hertfordshire
United Kingdom	Site GB44003	Sheffield
United States	Site US10045	Albuquerque	New Mexico
United States	Site US10050	Atlanta	Georgia
United States	Site US10013	Aventura	Florida
United States	Site US10042	Baton Rouge	Louisiana
United States	Site US10021	Bethlehem	Pennsylvania
United States	Site US10029	Beverly Hills	California
United States	Site US10034	Boston	Massachusetts
United States	Site US10025	Fountain Valley	California
United States	Site US10047	Glenwood Springs	Colorado
United States	Site US10036	La Jolla	California
United States	Site US10011	Lacey	Washington
United States	Site US10051	Loma Linda	California
United States	Site US10033	Los Angeles	California
United States	Site US10046	Milwaukee	Wisconsin
United States	Site US10030	Minneapolis	Minnesota
United States	Site US10012	Mount Kisco	New York
United States	Site US10009	Nashville	Tennessee
United States	Site US10023	Nashville	Tennessee
United States	Site US10031	Oxnard	California
United States	Site US10052	Redondo Beach	California
United States	Site US10027	Rochester	Minnesota
United States	Site US10048	Saint Petersburg	Florida
United States	Site US10003	Santa Monica	California
United States	Site US10037	Scarborough	Maine
United States	Site US10018	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Chile,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Peru,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)	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.	From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)
Secondary	Percentage of Deaths	All events of death after the first study drug administration were included.	From date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months)
Secondary	Percentage of Participants With Objective Response (OR)	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.	From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)
Secondary	PFS as Assessed by the Investigator	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.	From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)
Secondary	Percentage of Participants With Disease Control	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.	From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)
Secondary	Duration of Response (DOR)	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.	From date of first response up to data cut-off date 09 May 2017 (approximately 15 months)
Secondary	Number of Participants With Adverse Events (AEs)	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.	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
Secondary	Functional Assessment of Cancer Therapy - EGFR Inhibitors Subscale (FACT-EGFRI-18) Questionnaire	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).	Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
Secondary	European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC-QLQ-LC13)	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.	Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
Secondary	European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)	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.	Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)
Secondary	EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)	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).	Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

External Links

•   Link to results on the Astellas Clinical Study Results website