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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00863746
First received: March 17, 2009
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Carcinoma
Non-Small-Cell Lung
Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization of the first subject until 36 months later ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: From randomization of the first subject until 36 months later assessed every 6 weeks ] [ Designated as safety issue: No ]
    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.

  • Disease Control [ Time Frame: From randomization of the first subject until 36 months later assessed every 6 weeks ] [ Designated as safety issue: No ]
    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)].

  • Objective Tumor Response [ Time Frame: From randomization of the first subject until 36 months later assessed every 6 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to Progression [ Time Frame: From randomization of the first subject until 36 months later assessed every 6 weeks ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score [ Time Frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score [ Time Frame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle) ] [ Designated as safety issue: No ]
    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)


Enrollment: 703
Study Start Date: April 2009
Study Completion Date: April 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00863746

  Show 182 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00863746     History of Changes
Other Study ID Numbers: 13266, 2008-006914-62
Study First Received: March 17, 2009
Results First Received: April 10, 2013
Last Updated: April 17, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentosy Tecnologia Medica
Austria: Ethikkommission
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
China: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: German Institute of Medical Documentation and Information
Greece: Ethics Committee
Hong Kong: Department of Health
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
India: Drugs Controller General of India
Indonesia: National Agency of Drug and Food Control
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Japan: National Institute of Health Sciences
Korea: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Peru: Ministry of Health
United States: Food and Drug Administration
Singapore: Health Sciences Authority
Pakistan: Ministry of Health
Phillipines: Department of Health
Taiwan: Department of Health
Thailand: Food and Drug Administration
Hungry: National Institute of Pharmacy
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Turkey: Ethics Committee
Sweden: Ethikkommission
Spain: Spanish Agency of Medicines
Russia: Ethics Committee
South Africa: Human Research Ethics Committee
Poland: Ministry of Health

Keywords provided by Bayer:
Non-Small Cell Lung Cancer (NSCLC)
Sorafenib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014