A 3rd/4th Line Placebo-controlled Trial of Sorafenib in Patients With Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC). (MISSION)

A Phase III, Multi-center, Placebo-Controlled Trial of Sorafenib (BAY43-9006) in Patients With Relapsed or Refractory Advanced Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC) After 2 or 3 Previous Treatment Regimens for Advanced Disease

The purpose of the study is to see if sorafenib plus best supportive care (i.e. in addition to the non-cancer treatments patients would normally receive) is an effective treatment for lung cancer compared to best supportive care alone. The safety and tolerability of the two treatment groups will also be compared. The goal of the study is to test the ability of sorafenib to improve survival compared to best supportive care alone.

Study Overview

• Status: Completed
• Conditions: Carcinoma; Non-Small-Cell Lung
• Intervention / Treatment: Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Placebo

Detailed Description

Acronyms used in Adverse Events section: Disseminated intravascular coagulation (DIC), International normalized ratio (INR), Atrioventricular (AV), Gastrointestinal (GI), Not otherwise specified (NOS), Common Terminology Criteria for Adverse Events (CTCAE), Absolute neutrophil count (ANC), Central nervous system (CNS), Acute respiratory distress syndrome (ARDS), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST).

• Study Type: Interventional
• Enrollment (Actual): 703
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, 5000
  • Córdoba, Argentina, X5016KEH
  • Santa Fé, Argentina, S3000FFV
  • Buenos Aires
    • Ramos Mejía, Buenos Aires, Argentina, B1704ESN
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1430ERF
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
    • Rosario, Santa Fe, Argentina, S2000DSK
• Austria
  • Graz, Austria, 8036
  • Linz, Austria, 4010
  • Wien, Austria, 1090
• Belgium
  • Antwerpen, Belgium, 2020
  • Bruxelles - Brussel, Belgium, 1200
  • Charleroi, Belgium, 6000
  • Genk, Belgium, 3600
• Brazil
  • Sao Paulo, Brazil, 01224-010
  • Distrito Federal
    • Brasilia, Distrito Federal, Brazil, 70680-650
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-281
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
    • Porto Alegre, Rio Grande do Sul, Brazil, 90050 170
  • Sao Paulo
    • Santo André, Sao Paulo, Brazil, 09020 110
    • São José dos Campos, Sao Paulo, Brazil, 12245750
    • São Paulo, Sao Paulo, Brazil, 05651-900
• Bulgaria
  • Plovdiv, Bulgaria
  • Sofia, Bulgaria
  • Sofia, Bulgaria, 1784
  • Varna, Bulgaria, 9002
  • Varna, Bulgaria, 9010
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
• Chile
  • Santiago, Chile, 838-0456
  • Santiago, Chile, 838-0455
• China
  • Beijing, China, 100021
  • Beijing, China, 100142
  • Beijing, China, 100071
  • Beijing, China, 100853
  • Guangzhou, China, 510080
  • Shanghai, China, 200433
  • Shanghai, China, 200030
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
  • Sichuan
    • Chengdu, Sichuan, China, 610041
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
    • Hangzhou, Zhejiang, China, 310022
• France
  • Caen, France, 14073
  • Dijon, France, 21000
  • La Roche Sur Yon Cedex, France, 85025
  • La Tronche, France, 38700
  • Lille, France, 59020
  • Lyon Cedex, France, 69317
  • Saint Herblain, France, 44805
  • Tours, France, 37044
• Germany
  • Hamburg, Germany, 21075
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69126
    • Karlsruhe, Baden-Württemberg, Germany, 76137
    • Mannheim, Baden-Württemberg, Germany, 68167
    • Ulm, Baden-Württemberg, Germany, 89091
  • Bayern
    • Gauting, Bayern, Germany, 82131
    • München, Bayern, Germany, 80336
  • Hessen
    • Kassel, Hessen, Germany, 34125
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 51109
  • Schleswig-Holstein
    • Großhansdorf, Schleswig-Holstein, Germany, 22927
  • Thüringen
    • Bad Berka, Thüringen, Germany, 99437
• Greece
  • Athens, Greece, 11527
  • Heraklion, Greece, 711 10
  • Thessaloniki, Greece, 570 10
• Hong Kong
  • Hongkong, Hong Kong
  • Kowloon, Hong Kong
  • N.T
    • Shatin, N.T, Hong Kong
• Hungary
  • Budapest, Hungary, 1125
  • Budapest, Hungary, 1529
  • Edeleny, Hungary, 3780
  • Farkasgyepu, Hungary, 8582
  • Torokbalint, Hungary, 2045
  • Zalaegerszeg, Hungary, 8900
• India
  • Kerala, India, 682304
  • Maharashtra
    • Mumbai, Maharashtra, India, 422004
    • Pune, Maharashtra, India, 411001
• Indonesia
  • Bandung, Indonesia, 40161
  • Jakarta, Indonesia, 11420
• Israel
  • Holon, Israel
  • Jerusalem, Israel, 9112001
  • Jerusalem, Israel, 9372212
  • Kfar Saba, Israel, 4428164
  • Petach Tikva, Israel, 4941492
  • Zrifin, Israel, 6093000
• Italy
  • Avellino, Italy, 83100
  • Genova, Italy, 16132
  • Livorno, Italy, 57124
  • Parma, Italy, 43100
  • Perugia, Italy, 06156
  • Roma, Italy, 00151
  • Milano
    • Rozzano, Milano, Italy, 20089
  • Monza-Brianza
    • Monza, Monza-Brianza, Italy, 20052
  • Torino
    • Orbassano, Torino, Italy, 10043
• Japan
  • Fukuoka, Japan, 811-1395
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
    • Sakai, Osaka, Japan, 591-8555
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8606
    • Koto-ku, Tokyo, Japan, 135-8550
• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 135-710
  • Seoul, Korea, Republic of, 136-705
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 110-744
• Netherlands
  • Amsterdam, Netherlands, 1081HV
  • Harderwijk, Netherlands, 3844 DG
  • Heerlen, Netherlands, 6419 PC
  • Helmond, Netherlands, 5707 HA
  • Nieuwegein, Netherlands, 3435 CM
  • Zwolle, Netherlands, 8025 AB
• Pakistan
  • Punjab
    • Lahore, Punjab, Pakistan, 54000
  • Sindh
    • Karachi, Sindh, Pakistan, 74700
• Peru
  • Callao, Peru, CALLAO 2
  • Lima, Peru, Lima 27
  • Lima, Peru, Lima 11
  • Lima, Peru, Lima 1
  • Lima, Peru, LIMA 34
  • San Borja, Peru
• Philippines
  • Cebu City, Philippines, 6000
  • Manila, Philippines, 1000
  • Metro Manila, Philippines, 1000
  • Quezon City, Philippines, 1104
• Poland
  • Kielce, Poland, 25-316
  • Krakow, Poland, 31-115
  • Olsztyn, Poland, 10-357
  • Rzeszow, Poland, 35-021
  • Szczecin, Poland, 70-891
  • Warszawa, Poland, 01-138
• Russian Federation
  • Kazan, Russian Federation, 420029
  • Moscow, Russian Federation, 115478
  • Moscow, Russian Federation, 129128
  • Moscow, Russian Federation, 105 005
  • St. Petersburg, Russian Federation, 198255
  • Yaroslavl, Russian Federation, 150054
• Singapore
  • Singapore, Singapore, 119228
  • Singapore, Singapore, 308433
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
    • Prietoria, Gauteng, South Africa, 0084
  • Kwazulu-Natal
    • Durban, Kwazulu-Natal, South Africa, 4126
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08025
  • Lleida, Spain, 25198
  • Lugo, Spain, 27003
  • Madrid, Spain, 28040
  • Málaga, Spain, 29010
  • Sevilla, Spain, 41013
  • Zamora, Spain, 49021
  • Bilbao
    • Cruces/Barakaldo, Bilbao, Spain, 48903
  • Ourense
    • Orense, Ourense, Spain, 32005
• Sweden
  • Falun, Sweden, 791 82
  • Göteborg, Sweden, 413 45
  • Linköping, Sweden, 581 85
  • Lund, Sweden, 221 85
  • Stockholm, Sweden, 171 76
• Taiwan
  • Kaohsiung, Taiwan, 80756
  • Taichung, Taiwan, 404
  • Taichung, Taiwan, 40705
  • Taipei, Taiwan, 10016
  • Taoyuan, Taiwan, 333
• Thailand
  • Bangkok, Thailand, 10700
  • Chiang Mai, Thailand, 50200
  • Songkhla, Thailand, 90110
• Turkey
  • Ankara, Turkey
  • Instanbul, Turkey, 34662
  • Istanbul, Turkey
  • Izmir, Turkey
  • Kocaeli, Turkey, 41400
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • London, United Kingdom, SW3 6JJ
  • London, United Kingdom, NW3 2QG
  • Avon
    • Bristol, Avon, United Kingdom, BS10 5NB
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
  • Manchester
    • Greater Manchester, Manchester, United Kingdom, M20 4BX
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
  • California
    • Stanford, California, United States, 94305
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to understand and willingness to sign a written Informed Consent
• Advanced relapsed or refractory predominantly non squamous NSCLC. The diagnosis must have been confirmed cyto-/ histologically
• Patients must have measurable or non-measurable disease
• At least two but not more than three prior standard treatment regimens for NSCLC
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Male or female subjects >/= 18 years of age (>/=20 for Japan) at the time of Informed Consent
• Life expectancy of at least 12 weeks
• Ability to swallow oral medication
• Both men and women using adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of the study drug:

  • Haemoglobin > 9.0 g/dl
  • Absolute neutrophil count (ANC) >1,500/mm3
  • Platelet count >/= 100,000/µl
  • Total bilirubin </=1.5 x the upper limit of normal
  • Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases) Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases)
  • Alkaline phosphatase < 4 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases)
  • Prothrombin Time (PT)-International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal
  • Serum creatinine < 1.5 x upper limit of normal
  • Calculated creatinine clearance of >/= 50 mL/min

Exclusion Criteria:

• NSCLC patients with predominantly squamous cell carcinoma histology

Excluded medical conditions:

• History of cardiac disease: Congestive heart failure, Active coronary artery disease (CAD), Cardiac arrhythmias (>Grade 2 NCI-CTCAE [National Cancer Institute-Common Terminology Criteria for Adverse Events] vers. 3.0)
• Uncontrolled hypertension despite two anti-hypertensive medications
• History of Human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• History of organ allograft
• Active clinically serious infections (> grade 2 NCI-CTCAE vers. 3.0)
• Patients with seizure disorder requiring medication
• Patients with evidence or history of bleeding diathesis or coagulopathy
• Patients undergoing renal dialysis
• Pulmonary hemorrhage/ bleeding event >/= CTCAE grade 2 within four weeks prior to the first dose of the study drug
• Any other hemorrhage/ bleeding event >/= CTCAE grade 3 within four weeks prior to the first dose of the study drug
• Thrombotic or embolic venous or arterial events such as cerebrovascular accident
• Pregnant or breast-feeding women.
• Any condition which could affect the absorption or pharmacokinetics of the study drug
• Prior treatment with other Vascular Endothelial Growth Factor (VEGF) (R) inhibitors, including compounds that impact vascularity (i.e. sunitinib, thalidomide, vandetanib, vascular disrupting agents [VDA], VEGF-trap and other experimental agents of this class). Only bevacizumab (Avastin) is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib (Nexavar, BAY43-9006); Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (BID)	Drug: Sorafenib (Nexavar, BAY43-9006); Sorafenib 400 mg twice daily (BID)
Placebo Comparator: Placebo; Participants received 2 tablets of placebo orally twice daily (BID)	Drug: Placebo; Placebo - 2 tablets twice daily (BID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. Overall survival of subjects alive at the time of analysis will be censored at their last date of follow-up or database cut off date whichever came first.	From randomization of the first subject until 36 months later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival (PFS) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute progressive disease. In exceptional circumstances unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression.	From randomization of the first subject until 36 months later assessed every 6 weeks
Disease Control	Disease control (DC) was defined as the proportion of patients whose best response was Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)] or Partial Response [PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD] or Stable Disease [SD: steady state of disease which was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD)].	From randomization of the first subject until 36 months later assessed every 6 weeks
Objective Tumor Response	Objective tumor response was defined as the proportion of patients whose best response was Complete Response [CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target)] or Partial Response [PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD] over the whole duration of study.	From randomization of the first subject until 36 months later assessed every 6 weeks
Time to Progression	Time to progression (TTP) was defined as the time from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier).	From randomization of the first subject until 36 months later assessed every 6 weeks
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status	The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The 'Global Health status' subscale consists of question 15 of the questionnaire. The score of 'Global Health status' ranges from 0 (very poor) to 100 (excellent). The change of score ranges from -100 (maximum degree of worsening) to 100 (maximum degree of improvement).	Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale	A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The coughing subscale uses question 1 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems).	Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea	A clinically valid 13-item tool for assessing disease- and treatment-specific symptoms in lung cancer patients in clinical trials. The dyspnea subscale uses questions 3, 4 and 5 of the questionnaire. The scale ranges from 0 to 100. Higher score means higher level of symptomatology/problems. The change of score ranges from -100 (decrease in level of symptomatology/problems) to 100 (increase in level of symptomatology/problems).	Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score	The Euro-Qol 5D (EQ-5D) is a validated assessment tool of Health Related Quality of Life (HRQOL) and utilities consisting of 15 statements. Patients select those statements that best describe their current health state regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression which is converted into a utility value. Range of scale is from -0.594 (worst possible health state) to 1 (perfect health) based on UK weights. The change of score ranges from -1.594 (high degree of worsening) to 1.594 (high degree of improvement).	Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score	A visual analogue scale (EQ VAS) used by patients to rate their current health state from 100 (best imaginable health state) to 0 (worst imaginable health state). The change of score ranges from -100 (high degree of worsening) to 100 (high degree of improvement)	Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Estimate): January 19, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Sorafenib; Non-Small Cell Lung Cancer (NSCLC)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 13266; 2008-006914-62 (EudraCT Number)