Clinical trial NCT01529112: A Study Comparing the Combination of the Best Supportive Care Plus E7080 Versus Best Supportive Care Alone, in Patients With Advanced Lung Cancer or Lung Cancer That Has Spread, Who Have Been Previously Treated, Unsuccessfully, With at Least 2 Different Treatments
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Oral E7080 in Addition to Best Supportive Care (BSC) Versus BSC Alone in Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer Who Have Failed at Least Two Systemic Anticancer Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Locally Advanced
Metastatic Non-Squamous Non-Small Cell Lung Cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2012-02-08
Enrollment: 135
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 this study is to compare the overall survival of patients receiving E7080 + Best Supportive Care (BSC) with those receiving placebo + Best Supportive Care.

Detailed description: This double-blind, placebo-controlled, multicenter, randomized Phase II study will consist of a 2-arm design, comparing E7080 + BSC (Arm 1) with placebo + BSC (Arm 2). Participants will be randomized in the ratio of 2:1 to receive either E7080 or placebo in a blinded manner.

Eligibility criteria: Inclusion Criteria

1. Age greater than or equal to 18 years;
2. Participants with histologically or cytologically confirmed non-squamous NSCLC with locally advanced or metastatic disease based on Tumor, Node, Metastasis (TNM) staging according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Seventh Edition, who had failed at least two lines of systemic anticancer therapy for advanced or metastatic NSCLC (did not include adjuvant chemotherapy). In countries where erlotinib was approved and marketed for the treatment of NSCLC, participants must have received erlotinib treatment (or gefitinib for participants outside of the US) for their NSCLC if they had known EGFR-activating mutations. Participants of unknown EGFR status who had not received prior erlotinib (or gefitinib) should have been tested for EGFR-activating mutations prior to study entry. In countries where crizotinib was approved and marketed, participants must have received crizotinib treatment for NSCLC that was ALK-positive. Participants with ALK positive NCSLC or participants with KRAS mutations were not required to have prior treatment with erlotinib or gefitinib
3. Participants must have at least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1);
4. ECOG PS of 0 to 2;
5. Participants must have adequate renal function as evidenced by serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or calculated creatinine clearance greater than or equal to 30 mL/min per the Cockcroft and Gault formula;
6. Blood pressure must be well-controlled (less than or equal to140/90 mm Hg at Screening) with or without antihypertensive medication. Participants must have no history of hypertensive crisis or hypertensive encephalopathy;
7. Participants must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than or equal to 9.0 g/dL, and platelet count greater than or equal to 100 x 109/L;
8. Participants must have adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the ULN, and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases, less than or equal to 5 x ULN).
9. Participants must have adequate coagulation system function as defined by prothrombin time/International normalized ratio (INR) less than or equal to 1.5 x ULN.
10. Male or female participants of child-producing potential must agree to use double barrier contraception, oral contraceptives, or avoidance of pregnancy measures during the study and for 90 days after the last day of treatment;
11. Females of childbearing potential must have a negative serum pregnancy test;
12. Females may not be breastfeeding;
13. Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria

1. Prior therapy with E7080 or other small molecule vascular endothelial growth factor inhibitors;
2. Presence of brain metastases, unless the participant has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization;
3. Meningeal carcinomatosis;
4. Received chemotherapy, targeted therapy, radiotherapy, surgery, or immunotherapy within the 21 days prior to commencing study treatment or have not recovered from all treatment-related toxicities to Grade less than or equal to 2, except for alopecia;
5. Received treatment with another investigational agent within the 30 days prior to commencing study treatment or participants who have not recovered from side effects of an investigational drug to Grade less than or equal to 2, except for alopecia;
6. Participants with proteinuria greater than 1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with 24-hour urine protein greater than or equal to 1 g/24 hours will be ineligible;
7. Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury within the 28 days prior to commencing study treatment.
8. Major surgery scheduled during the projected course of the study;
9. History of bleeding diathesis or coagulopathy;
10. Active hemoptysis (defined as bright red blood of a half teaspoon or more) within the 30 days prior to study entry;
11. Refractory nausea and vomiting, malabsorption, significant bowel resection, or any other medical condition that would preclude adequate absorption or result in the inability to take oral medication;
12. Other malignancy within 3 years of randomization, with the exception of adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer, with no subsequent evidence of recurrence and/or malignancies diagnosed at a stage where definitive therapy results in near certain cures.
13. Significant cardiovascular impairment (history of congestive heart failure New York Heart Association \[NYHA\] Class greater than II, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
14. Any history of cerebral vascular accident (CVA), transient ischemic attack (TIA), or Grade greater than or equal to 2 peripheral vascular disease unless they have had no evidence of active disease for at least 6 months prior to randomization;
15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the 6 months prior to enrollment;
16. Participants with organ allografts requiring immunosuppression;
17. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive;
18. Hypersensitivity to E7080 or any of the excipients;
19. Any history of or concomitant medical condition that, in the opinion of the Investigator, would compromise the participant's ability to safely complete the study.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomization (Day 1) until occurrence of 90 deaths in the study (cut off date 26 November 2013), approximately 22 months
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Non-serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: For each participant, from the first dose till 30 days after the last dose or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: 6-Month Survival Rate
timeFrame: From date of randomization (Day 1) up to 6 months
measure: 1-year Survival Rate
timeFrame: From date of randomization (Day 1) up to 1 year
measure: Progression-Free Survival (PFS)
timeFrame: From date of randomization (Day 1) until date of first documentation of disease progression or death from any cause (whichever occurred first) or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: Overall Response Rate (ORR)
timeFrame: From date of randomization (Day 1) until disease progression or death, development of unacceptable toxicity, withdrawal of consent, withdrawal by Investigator, or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: Response Duration (RD)
timeFrame: From date of randomization (Day 1) until disease progression or death, development of unacceptable toxicity, withdrawal of consent, withdrawal by Investigator, or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: Disease Control Rate (DCR)
timeFrame: From date of randomization (Day 1) until disease progression or death, development of unacceptable toxicity, withdrawal of consent, withdrawal by Investigator, or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: The Percentage of Participants With The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Symptom Scores Achieving Clinically Significant Deterioration on Quality of Life (QOL)
timeFrame: Baseline (Day 1 of Cycle 1 (prior to treatment in Cycle 1)), every 4 weeks during treatment, and 4 weeks after completing treatment or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: The Percentage of Participants With The European Organization for Research and Treatment of Cancer (EORTC) Module QLQ-LC13 (Lung Cancer 13) Symptom Scores Achieving Clinically Significant Deterioration on QOL
timeFrame: Baseline (Day 1 of Cycle 1 (prior to treatment in Cycle 1)), every 4 weeks during treatment, and 4 weeks after completing treatment or up to approximately 2 years (data cut-off date of 21 January 2014)
measure: Pharmacokinetic (PK) Profile of Lenvatinib in Subjects With Non Small Cell Lung Cancer (NSCLC)
timeFrame: Cycle 1/Day 1 (between 0.5 and 4 hours postdose and 6 and 10 hours postdose), Cycle 1/Day 15 (predose, between 0.5 and 4 hours postdose, and 6 and 10 hours postdose), and Day 1 of Cycles 2 though 4 (predose and between 2 and 12 hours postdose)
Other outcomes:
Locations:
city: Casa Grande
country: United States
facility: Donald W. Hill, M.D., F.A.C.P.
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates , PC - HOPE
state: Arizona
city: Gilroy
country: United States
facility: Ronald Yanagihara, MD 9360 North Name Uno Suite 130 Gilroy California 95020
state: California
city: Ocala
country: United States
facility: Ocala Oncology Center, P.L.
state: Florida
city: Saint Louis
country: United States
facility: Washington University 660 South Euclid Avenue Campus Box 8124 St Louis Missouri 63110
state: Missouri
city: Clifton Park
country: United States
facility: New York Oncology Heamatology - Latham
state: New York
city: New York
country: United States
facility: Montefiore Medical Park 1695 Easchester Road Floor 1 Bronx, NY 10461
state: New York
city: Bismarck
country: United States
facility: Cancer Treatment and Research Centre Bismarck North Dakota 58501
state: North Dakota
city: Paris
country: United States
facility: Texas Oncology, P.A. - Paris
state: Texas
city: Plano
country: United States
facility: Texas Oncology, P.A. - Plano
state: Texas
city: Waco
country: United States
facility: Texas Oncology, P.A. - Waco
state: Texas
city: Aalst
country: Belgium
facility: OLV Ziekenhuis
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Duffel
country: Belgium
facility: AZ Sint-Maarten
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: C. H. R. de la Citadelle
city: Liege
country: Belgium
facility: Domaine Universitaire du Sart-Tilman
city: Nova Ves pod Plesi
country: Czechia
facility: Institut onkologie a rehabilitace Na Plesi
city: Nymburk
country: Czechia
facility: Avicennus, s.r.o.
city: Praha 8
country: Czechia
facility: Fakultni nemocnice Na Bulovce
city: Pribram
country: Czechia
facility: Oblastni nemocnice Pribram, a.s.
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK
city: Budapest
country: Hungary
facility: Orszagos Koranyi TBC es Pulmonologiai Intezet
city: Matrahaza
country: Hungary
facility: Matrai Gyogyintezet
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Korhaz
city: Tatabanya
country: Hungary
facility: Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Korhaz
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Milano
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri IRCCS
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Verona
country: Italy
facility: Ospedale Mater Salutis
city: Chungcheongbuk-do
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Yeouido St. Mary's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Stoke-on-Trent
country: United Kingdom
facility: North Staffs Royal Infirmary
state: Staffordshire
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Strathclyde
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: West Midlands
Study officials:
affiliation: PharmaBio Development Inc.
name: Harish Dave
role: STUDY_DIRECTOR
References: