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

NCT01529112 | Completed Phase 2 Results DMC

• 1 other identifier: E7080-703
• Study Type: interventional
• Target: 135
• Locations: 7 countries
• Sites: 50

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Locally Advanced; Metastatic Non-Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time from the date of randomization until the date of death from any cause.

  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 (10)

• Number of Participants With Treatment Emergent Non-serious Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)

  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)

• 6-Month Survival Rate

  From date of randomization (Day 1) up to 6 months

• 1-year Survival Rate

  From date of randomization (Day 1) up to 1 year

• Progression-Free Survival (PFS)

  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)

• Overall Response Rate (ORR)

  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)

Study Arms (2)

Lenvatinib

EXPERIMENTAL

Participants received lenvatinib 24 mg orally, once daily continuously in each 28-day treatment cycle plus Best Supportive Care (BSC)

Drug: Lenvatinib; Drug: BSC

Lenvatinib matched placebo

PLACEBO COMPARATOR

Participants received lenvatinib matched placebo orally, once daily continuously in each 28-day treatment cycle plus BSC

Drug: Lenvatinib matched placebo; Drug: BSC

Interventions

Lenvatinib DRUG

Also known as: E7080

Lenvatinib

Lenvatinib matched placebo DRUG

Lenvatinib matched placebo

BSC DRUG

Lenvatinib; Lenvatinib matched placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years;
• 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
• 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);
• ECOG PS of 0 to 2;
• 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;
• 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;
• 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;
• 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).
• 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.
• 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;
• Females of childbearing potential must have a negative serum pregnancy test;
• Females may not be breastfeeding;
• Ability to understand and willingness to sign a written informed consent.

You may not qualify if:

• Prior therapy with E7080 or other small molecule vascular endothelial growth factor inhibitors;
• 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;
• Meningeal carcinomatosis;
• 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;
• 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;
• 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;
• 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.
• Major surgery scheduled during the projected course of the study;
• History of bleeding diathesis or coagulopathy;
• Active hemoptysis (defined as bright red blood of a half teaspoon or more) within the 30 days prior to study entry;
• 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;
• 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.
• 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);
• 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;
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the 6 months prior to enrollment;

Sponsors & Collaborators

• Eisai Inc.: lead
• Quintiles, Inc.: collaborator

Study Sites (50)

Donald W. Hill, M.D., F.A.C.P.

Casa Grande, Arizona, 85122, United States

Location

Arizona Oncology Associates , PC - HOPE

Tucson, Arizona, 85710, United States

Location

Ronald Yanagihara, MD 9360 North Name Uno Suite 130 Gilroy California 95020

Gilroy, California, 95020, United States

Location

Ocala Oncology Center, P.L.

Ocala, Florida, 34471, United States

Location

Washington University 660 South Euclid Avenue Campus Box 8124 St Louis Missouri 63110

St Louis, Missouri, 63110, United States

Location

New York Oncology Heamatology - Latham

Clifton Park, New York, 12065, United States

Location

Montefiore Medical Park 1695 Easchester Road Floor 1 Bronx, NY 10461

New York, New York, 10467, United States

Location

Cancer Treatment and Research Centre Bismarck North Dakota 58501

Bismarck, North Dakota, 58501, United States

Location

Texas Oncology, P.A. - Paris

Paris, Texas, 75460, United States

Location

Texas Oncology, P.A. - Plano

Plano, Texas, 75093, United States

Location

Texas Oncology, P.A. - Waco

Waco, Texas, 76712, United States

Location

OLV Ziekenhuis

Aalst, 9300, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

AZ Sint-Maarten

Duffel, 2570, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

C. H. R. de la Citadelle

Liège, 4000, Belgium

Location

Domaine Universitaire du Sart-Tilman

Liège, 4000, Belgium

Location

Institut onkologie a rehabilitace Na Plesi

Nová Ves pod Pleší, Czechia

Location

Avicennus, s.r.o.

Nymburk, Czechia

Location

Fakultni nemocnice Na Bulovce

Prague, Czechia

Location

Oblastni nemocnice Pribram, a.s.

Příbram, Czechia

Location

Semmelweis Egyetem AOK

Budapest, 1125, Hungary

Location

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, 1529, Hungary

Location

Matrai Gyogyintezet

Mátraháza, 3233, Hungary

Location

Fejer Megyei Szent Gyorgy Korhaz

Székesfehérvár, 8000, Hungary

Location

Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza

Tatabánya, 2800, Hungary

Location

Tudogyogyintezet Torokbalint

Törökbálint, 2045, Hungary

Location

Zala Megyei Korhaz

Zalaegerszeg, 8900, Hungary

Location

Azienda Ospedaliera G. Rummo

Benevento, 82100, Italy

Location

Azienda Ospedaliero Universitaria San Martino

Genova, 16132, Italy

Location

Azienda Ospedaliera San Gerardo

Milan, 20052, Italy

Location

Istituto Clinico Humanitas

Milan, 20089, Italy

Location

Azienda Ospedaliera Universitaria di Parma

Parma, 43100, Italy

Location

Fondazione Salvatore Maugeri IRCCS

Pavia, 27100, Italy

Location

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, 6156, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Roma, 149, Italy

Location

Ospedale Mater Salutis

Verona, 37045, Italy

Location

Chungbuk National University Hospital

Chungcheongbuk-do, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun-gun, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

The Catholic University of Korea Yeouido St. Mary's Hospital

Seoul, South Korea

Location

Ulsan University Hospital

Ulsan, South Korea

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Location

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Location

North Staffs Royal Infirmary

Stoke-on-Trent, Staffordshire, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Strathclyde, United Kingdom

Location

New Cross Hospital

Wolverhampton, West Midlands, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• Harish Dave

  PharmaBio Development Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2012
• First Posted: February 8, 2012
• Study Start: November 1, 2011
• Primary Completion: January 21, 2014
• Study Completion: June 27, 2015
• Last Updated: September 26, 2017
• Results First Posted: February 18, 2016

Record last verified: 2017-08

Locations

KR (7); BE (7); GB (5); IT (9); US (11); CZ (4); HU (7)