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

NCT ID: NCT01529112

Last Updated: 2017-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-06-27

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lenvatinib

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

Group Type: EXPERIMENTAL

Lenvatinib

Intervention Type: DRUG

BSC

Intervention Type: DRUG

Lenvatinib matched placebo

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

Group Type: PLACEBO_COMPARATOR

Lenvatinib matched placebo

Intervention Type: DRUG

BSC

Intervention Type: DRUG

Interventions

Lenvatinib

Intervention Type: DRUG

Lenvatinib matched placebo

Intervention Type: DRUG

BSC

Intervention Type: DRUG

Other Intervention Names

E7080

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harish Dave

Role: STUDY_DIRECTOR

PharmaBio Development Inc.

Locations

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

Casa Grande, Arizona, United States

Arizona Oncology Associates , PC - HOPE

Tucson, Arizona, United States

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

Gilroy, California, United States

Ocala Oncology Center, P.L.

Ocala, Florida, United States

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

St Louis, Missouri, United States

New York Oncology Heamatology - Latham

Clifton Park, New York, United States

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

New York, New York, United States

Cancer Treatment and Research Centre Bismarck North Dakota 58501

Bismarck, North Dakota, United States

Texas Oncology, P.A. - Paris

Paris, Texas, United States

Texas Oncology, P.A. - Plano

Plano, Texas, United States

Texas Oncology, P.A. - Waco

Waco, Texas, United States

OLV Ziekenhuis

Aalst, , Belgium

Grand Hopital de Charleroi

Charleroi, , Belgium

AZ Sint-Maarten

Duffel, , Belgium

UZ Antwerpen

Edegem, , Belgium

UZ Leuven

Leuven, , Belgium

C. H. R. de la Citadelle

Liège, , Belgium

Domaine Universitaire du Sart-Tilman

Liège, , Belgium

Institut onkologie a rehabilitace Na Plesi

Nová Ves pod Pleší, , Czechia

Avicennus, s.r.o.

Nymburk, , Czechia

Fakultni nemocnice Na Bulovce

Prague, , Czechia

Oblastni nemocnice Pribram, a.s.

Příbram, , Czechia

Semmelweis Egyetem AOK

Budapest, , Hungary

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, , Hungary

Matrai Gyogyintezet

Mátraháza, , Hungary

Fejer Megyei Szent Gyorgy Korhaz

Székesfehérvár, , Hungary

Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza

Tatabánya, , Hungary

Tudogyogyintezet Torokbalint

Törökbálint, , Hungary

Zala Megyei Korhaz

Zalaegerszeg, , Hungary

Azienda Ospedaliera G. Rummo

Benevento, , Italy

Azienda Ospedaliero Universitaria San Martino

Genova, , Italy

Azienda Ospedaliera San Gerardo

Milan, , Italy

Istituto Clinico Humanitas

Milan, , Italy

Azienda Ospedaliera Universitaria di Parma

Parma, , Italy

Fondazione Salvatore Maugeri IRCCS

Pavia, , Italy

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, , Italy

Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Ospedale Mater Salutis

Verona, , Italy

Chungbuk National University Hospital

Chungcheongbuk-do, , South Korea

Chonnam National University Hwasun Hospital

Hwasun-gun, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

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

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

The Christie NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Southampton General Hospital

Southampton, Hampshire, United Kingdom

North Staffs Royal Infirmary

Stoke-on-Trent, Staffordshire, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, Strathclyde, United Kingdom

New Cross Hospital

Wolverhampton, West Midlands, United Kingdom

Countries

United States; Belgium; Czechia; Hungary; Italy; South Korea; United Kingdom

Other Identifiers

E7080-703

Identifier Type: -

Identifier Source: org_study_id