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A Phase III Randomized, Double-blind, Placebo Controlled Trial Comparing the Efficacy of Gemcitabine, Cisplatin and Sorafenib to Gemcitabine, Cisplatin and Placebo in First-Line Treatment of Patients With Stage IIIb With Effusion and Stage IV Non-Small Cell Lung Cancer (NSCLC) (NEXUS)

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006)
Placebo
Gemcitabine
Cisplatin
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring Non-Small Cell Lung Cancer (NSCLC), Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age > 18 years old
  • Stage IIIB (with cytologically confirmed malignant pleural or pericardial effusion) or Stage IV histological or cytological confirmation of NSCLC of non-squamous cell carcinoma subtype. (thoracentesis or pericardiocentesis is not necessary if a biopsy of the original tumor is available to confirm diagnosis of NSCLC).
  • Patients with at least one measurable lesion. Lesions must be measured by CT-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST, see Appendix 10.3)
  • Life expectancy of at least 12 weeks
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose:
  • Hemoglobin >/= 9.0 g/dl (>/= 5.6 mmol/l)
  • Absolute neutrophil count (ANC) >/= 1,500/mm3
  • Platelet count >/= 100,000/µl
  • Total bilirubin </= 1.5 x upper limit of normal
  • Alanine transaminase (ALT) and Aspartate transaminase (AST) </= 2.5 x upper limit of normal (</= 5 x upper limit of normal for patients with liver involvement of their cancer)
  • Alkaline Phosphatase </= 4 x upper limit of normal
  • PT-INR (Prothrombin Time - International Normalized Ratio) (international normalized ratio of PT) /PTT (Partial Thromboplastin Time) < 1.5 x upper limit of normal
  • Serum Creatinine </= 1.5 times the upper limit of normal and Serum Creatinine Clearance >/= 70ml/min
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Exclusion Criteria:

  • Excluded medical conditions:

    • Cardiac disease: Congestive heart failure > class II NYHA (New York Heart Association). Patients must not have unstable angina (anginal symptoms at rest) or active coronary artery disease (CAD), or myocardial infarction within the past 6 months
    • Cardiac arrhythmias requiring anti-arrhythmic therapy
    • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
    • History of HIV (Human immunodeficiency virus) infection or chronic hepatitis B or C
    • Active clinically serious infections (> grade 2 NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0)
    • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
    • Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis.
    • History of organ allograft
    • Patients with evidence or history of bleeding diathesis or coagulopathy
    • Patients undergoing renal dialysis
    • Cancer other than NSCLC within 5 years prior to start of study treatment EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumors [Ta (Noninvasive tumor), Tis (Carcinoma in situ) & T1 (Tumor invades lamina propria)]
    • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
    • Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
    • Pulmonary hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug
    • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
    • Serious, non-healing wound, ulcer, or bone fracture
    • Uncorrected dehydration
    • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
    • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
    • Known or suspected allergy to the investigational agent or any agent given in association with this trial
    • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
    • Patients unable to swallow oral medications
    • Any malabsorption condition
    • Patients with a hearing impairment (FOR GERMANY ONLY)
    • NSCLC patients with squamous cell carcinoma diagnosis documented either by cytology or biopsy.

  • Excluded therapies and medications, previous and concomitant:

    • Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for NSCLC
    • Concomitant use of nephrotoxic drugs, ototoxic drugs, anticonvulsant, anti-gout treatment
    • Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section)
    • Radiotherapy during study or within 4 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section) (FOR FRANCE ONLY)
    • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug (bronchoscopy is allowed)
    • Granulocyte colony stimulating factor (GCSF) or Granulocyte macrophage colony stimulating factor (GMCSF), within 3 weeks of study entry (these growth factors may be used during the study thereafter).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sorafenib (Nexavar, BAY43-9006) + GC

Placebo + GC

Arm Description

Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with sorafenib. Day 1: gemcitabine 1250 mg/ m^2 infusion (IV), followed by cisplatin 75 mg/ m^2 IV; Day 8: gemcitabine 1250 mg/ m^2 IV; Days 1-21: sorafenib 2 tablets (200 mg) taken orally (po) twice daily (bid). If the patient had radiological evidence of stable disease (SD) or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which sorafenib was administered 400 mg bid until criteria for withdrawal were met.

Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with placebo. Day 1: gemcitabine 1250 mg/ m^2 infusion (IV), followed by cisplatin 75 mg/ m^2 IV; Day 8: gemcitabine 1250 mg/ m^2 IV; Days 1-21: placebo 2 tablets po bid. If the patient had radiological evidence of SD or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which 2 placebo tablets were administered bid until criteria for withdrawal were met.

Outcomes

Primary Outcome Measures

Overall Survival (OS) in the ITT (Non-squamous) Population
Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.

Secondary Outcome Measures

OS in the ITT (Both Squamous and Non-squamous) Population
OS was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.
OS in the ITT (Squamous) Population
OS was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.
Progression-free Survival (PFS) in the ITT (Non-squamous) Population
PFS was defined as the time from date of randomization to disease progression (radiological or clinical, whichever was earlier, based on Investigator-assessment using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0) or death due to any cause, whichever occured first. Patients without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.
Time to Progression (TTP) in the ITT (Non-squamous) Population
TTP was defined as the time from date of randomization to disease progression (radiological or clinical, whichever was earlier, based on Investigator-assessment using RECIST version 1.0). Patients without progression at the time of analysis or death before progression were censored at their last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.
Percentage of Participants With Different Tumor Response in the ITT (Non-squamous) Population
Tumor response (= Best Overall Response) of a patient was defined as the best tumor response (confirmed Complete Response (CR: disappearance of tumor lesions), confirmed Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes), Stable Disease (SD: steady state of disease), or Progressive Disease (PD: an increase in the sum of tumor lesions sizes or new lesions)) observed during trial period assessed according to the RECIST criteria (version 1.0) based on Investigator-assessment.
Disease Control (DC) in the ITT (Non-squamous) Population
DC was defined as the total number of patients whose best response was not PD according to RECIST (version 1.0) by Investigator-assessment (= total number of CR + total number of PR + total number of SD; CR or PR had to be maintained for at least 28 days from the first demonstration of that rating, SD had to be documented at least once more than 6 weeks from baseline). PD: an increase in the sum of tumor lesions sizes or new lesions.
Duration of Response in the ITT (Non-squamous) Population
Duration of response was defined as the time from date of first documented objective response of PR or CR, whichever was noted earlier, to date of disease progression or death (if death occurred before progression was documented). Patients without disease progression at the time of analysis or death before progression were censored at the last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.
Duration of Stable Disease (SD) in the ITT (Non-squamous) Population
Duration of SD was defined as the time from date of randomization to date that disease progression (radiological or clinical, whichever was earlier) was first documented. Patients without disease progression at the time of analysis or death before progression were censored at the date of their last tumor assessment.(Disease progression: increase in the sum of tumor lesion sizes or new lesions.) Duration of stable disease was only evaluated in patients failing to achieve a best response of CR or PR.
Time to Response (TTR) in the ITT (Non-squamous) Population
TTR for patients who achieved a best response (CR or PR) was defined as the time from date of randomization to the earliest date that response was first documented.
Functional Assessment of Cancer Treatment-Lung (FACT-L) Scores in the ITT (Non-squamous) Population
The FACT-L measures health related quality of life (HRQOL) and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better HRQOL.
Lung Cancer Subscale (LCS) Scores in the ITT (Non-squamous) Population
LCS is a subscale of FACT-L measuring lung cancer specific symptoms. The LCS scores range from 0 to 28, higher scores represent fewer lung cancer symptoms.
Time to Symptomatic Deterioration (TSD) in the ITT (Non-squamous) Population
TSD is defined as the time from randomization to the date of symptomatic deterioration (≥3 point decline in the LCS score that is maintained for at least 2 consecutive cycles) or death if death occurs before these 2 consecutive cycles are completed.
Euro Quality of Life - 5D (EQ-5D) Index Scores in the ITT (Non-squamous) Population
The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 to 1 when the United Kingdom (UK) weights are applied (0=death, 1=perfect health). Higher index scores represent better health states.
EQ-5D Visual Analog Scale (VAS) Scores in the ITT (Non-squamous) Population
The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

Full Information

First Posted
March 16, 2007
Last Updated
April 3, 2015
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00449033
Brief Title
A Phase III Randomized, Double-blind, Placebo Controlled Trial Comparing the Efficacy of Gemcitabine, Cisplatin and Sorafenib to Gemcitabine, Cisplatin and Placebo in First-Line Treatment of Patients With Stage IIIb With Effusion and Stage IV Non-Small Cell Lung Cancer (NSCLC)
Acronym
NEXUS
Official Title
A Phase III Randomized, Double-blind, Placebo Controlled Trial Comparing the Efficacy of Gemcitabine, Cisplatin and Sorafenib to Gemcitabine, Cisplatin and Placebo in First-Line Treatment of Patients With Stage IIIb With Effusion and Stage IV Non-Small Cell Lung Cancer (NSCLC)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Evaluation of gemcitabine and cisplatin in combination with either sorafenib or placebo for the treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC)
Detailed Description
During follow-up, it was determined that there was one additional patient on placebo that was still receiving treatment as of 06 APR 2010 and therefore 10 patients' data are reported in the current CSR addendum, 6 in the sorafenib + GC group and 4 in the placebo + GC group, and as before all in the ITT (non-squamous) population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung
Keywords
Non-Small Cell Lung Cancer (NSCLC), Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
904 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib (Nexavar, BAY43-9006) + GC
Arm Type
Experimental
Arm Description
Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with sorafenib. Day 1: gemcitabine 1250 mg/ m^2 infusion (IV), followed by cisplatin 75 mg/ m^2 IV; Day 8: gemcitabine 1250 mg/ m^2 IV; Days 1-21: sorafenib 2 tablets (200 mg) taken orally (po) twice daily (bid). If the patient had radiological evidence of stable disease (SD) or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which sorafenib was administered 400 mg bid until criteria for withdrawal were met.
Arm Title
Placebo + GC
Arm Type
Placebo Comparator
Arm Description
Up to 6 cycles (21 days per cycle) of gemcitabine (G) and cisplatin (C) with placebo. Day 1: gemcitabine 1250 mg/ m^2 infusion (IV), followed by cisplatin 75 mg/ m^2 IV; Day 8: gemcitabine 1250 mg/ m^2 IV; Days 1-21: placebo 2 tablets po bid. If the patient had radiological evidence of SD or better after completing up to 6 cycles in the Chemotherapy Phase, the patient could continue to Maintenance Phase, during which 2 placebo tablets were administered bid until criteria for withdrawal were met.
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006)
Intervention Description
Multikinase inhibitor, Sorafenib 400 mg po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m^2 IV, Cisplatin 75 mg/m^2 IV
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 2 tablets po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m^2 IV, Cisplatin 75 mg/m^2 IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Chemotherapy component; Gemcitabine 1250 mg/m^2 IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Chemotherapy component; Cisplatin 75 mg/m^2 IV
Primary Outcome Measure Information:
Title
Overall Survival (OS) in the ITT (Non-squamous) Population
Description
Overall survival (OS) was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.
Time Frame
from randomization of the first patient until 38 months or date of death of any cause whichever came first
Secondary Outcome Measure Information:
Title
OS in the ITT (Both Squamous and Non-squamous) Population
Description
OS was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.
Time Frame
from randomization of the first patient until 38 months or date of death of any cause whichever came first
Title
OS in the ITT (Squamous) Population
Description
OS was defined as the time from date of randomization to death due to any cause. Patients still alive at the time of analysis were censored at their last date of last contact.
Time Frame
from randomization of the first patient until 38 months or date of death of any cause whichever came first
Title
Progression-free Survival (PFS) in the ITT (Non-squamous) Population
Description
PFS was defined as the time from date of randomization to disease progression (radiological or clinical, whichever was earlier, based on Investigator-assessment using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0) or death due to any cause, whichever occured first. Patients without progression or death at the time of analysis were censored at their last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.
Time Frame
from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks
Title
Time to Progression (TTP) in the ITT (Non-squamous) Population
Description
TTP was defined as the time from date of randomization to disease progression (radiological or clinical, whichever was earlier, based on Investigator-assessment using RECIST version 1.0). Patients without progression at the time of analysis or death before progression were censored at their last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.
Time Frame
from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks
Title
Percentage of Participants With Different Tumor Response in the ITT (Non-squamous) Population
Description
Tumor response (= Best Overall Response) of a patient was defined as the best tumor response (confirmed Complete Response (CR: disappearance of tumor lesions), confirmed Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes), Stable Disease (SD: steady state of disease), or Progressive Disease (PD: an increase in the sum of tumor lesions sizes or new lesions)) observed during trial period assessed according to the RECIST criteria (version 1.0) based on Investigator-assessment.
Time Frame
from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks
Title
Disease Control (DC) in the ITT (Non-squamous) Population
Description
DC was defined as the total number of patients whose best response was not PD according to RECIST (version 1.0) by Investigator-assessment (= total number of CR + total number of PR + total number of SD; CR or PR had to be maintained for at least 28 days from the first demonstration of that rating, SD had to be documented at least once more than 6 weeks from baseline). PD: an increase in the sum of tumor lesions sizes or new lesions.
Time Frame
from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks
Title
Duration of Response in the ITT (Non-squamous) Population
Description
Duration of response was defined as the time from date of first documented objective response of PR or CR, whichever was noted earlier, to date of disease progression or death (if death occurred before progression was documented). Patients without disease progression at the time of analysis or death before progression were censored at the last date of tumor evaluation. Disease progression: increase in the sum of tumor lesion sizes or new lesions.
Time Frame
from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks
Title
Duration of Stable Disease (SD) in the ITT (Non-squamous) Population
Description
Duration of SD was defined as the time from date of randomization to date that disease progression (radiological or clinical, whichever was earlier) was first documented. Patients without disease progression at the time of analysis or death before progression were censored at the date of their last tumor assessment.(Disease progression: increase in the sum of tumor lesion sizes or new lesions.) Duration of stable disease was only evaluated in patients failing to achieve a best response of CR or PR.
Time Frame
from randomization of the first patient until 38 months or date of death or progression whichever came first, assessed until discontinuation every 6 weeks up to 9 months and then every 12 weeks
Title
Time to Response (TTR) in the ITT (Non-squamous) Population
Description
TTR for patients who achieved a best response (CR or PR) was defined as the time from date of randomization to the earliest date that response was first documented.
Time Frame
from randomization of the first patient until 38 months or date of death of any cause whichever came first
Title
Functional Assessment of Cancer Treatment-Lung (FACT-L) Scores in the ITT (Non-squamous) Population
Description
The FACT-L measures health related quality of life (HRQOL) and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better HRQOL.
Time Frame
from randomization of the first patient until 38 months
Title
Lung Cancer Subscale (LCS) Scores in the ITT (Non-squamous) Population
Description
LCS is a subscale of FACT-L measuring lung cancer specific symptoms. The LCS scores range from 0 to 28, higher scores represent fewer lung cancer symptoms.
Time Frame
from randomization of the first patient to 38 months later or death whatever occurs first.
Title
Time to Symptomatic Deterioration (TSD) in the ITT (Non-squamous) Population
Description
TSD is defined as the time from randomization to the date of symptomatic deterioration (≥3 point decline in the LCS score that is maintained for at least 2 consecutive cycles) or death if death occurs before these 2 consecutive cycles are completed.
Time Frame
from randomization of the first patient to 38 months later or death whatever occurs first
Title
Euro Quality of Life - 5D (EQ-5D) Index Scores in the ITT (Non-squamous) Population
Description
The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. These five health dimensions are summarized into a single score, the EQ-5D index score which ranges from -0.594 to 1 when the United Kingdom (UK) weights are applied (0=death, 1=perfect health). Higher index scores represent better health states.
Time Frame
from randomization of the first patient until 38 months later or death whatever occurs first
Title
EQ-5D Visual Analog Scale (VAS) Scores in the ITT (Non-squamous) Population
Description
The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame
from randomization of the first patient until 38 months later or death whatever occurs first

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age > 18 years old Stage IIIB (with cytologically confirmed malignant pleural or pericardial effusion) or Stage IV histological or cytological confirmation of NSCLC of non-squamous cell carcinoma subtype. (thoracentesis or pericardiocentesis is not necessary if a biopsy of the original tumor is available to confirm diagnosis of NSCLC). Patients with at least one measurable lesion. Lesions must be measured by CT-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST, see Appendix 10.3) Life expectancy of at least 12 weeks Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose: Hemoglobin >/= 9.0 g/dl (>/= 5.6 mmol/l) Absolute neutrophil count (ANC) >/= 1,500/mm3 Platelet count >/= 100,000/µl Total bilirubin </= 1.5 x upper limit of normal Alanine transaminase (ALT) and Aspartate transaminase (AST) </= 2.5 x upper limit of normal (</= 5 x upper limit of normal for patients with liver involvement of their cancer) Alkaline Phosphatase </= 4 x upper limit of normal PT-INR (Prothrombin Time - International Normalized Ratio) (international normalized ratio of PT) /PTT (Partial Thromboplastin Time) < 1.5 x upper limit of normal Serum Creatinine </= 1.5 times the upper limit of normal and Serum Creatinine Clearance >/= 70ml/min Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to performing any study specific procedures. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Exclusion Criteria: Excluded medical conditions: Cardiac disease: Congestive heart failure > class II NYHA (New York Heart Association). Patients must not have unstable angina (anginal symptoms at rest) or active coronary artery disease (CAD), or myocardial infarction within the past 6 months Cardiac arrhythmias requiring anti-arrhythmic therapy Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management. History of HIV (Human immunodeficiency virus) infection or chronic hepatitis B or C Active clinically serious infections (> grade 2 NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0) Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis. History of organ allograft Patients with evidence or history of bleeding diathesis or coagulopathy Patients undergoing renal dialysis Cancer other than NSCLC within 5 years prior to start of study treatment EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumors [Ta (Noninvasive tumor), Tis (Carcinoma in situ) & T1 (Tumor invades lamina propria)] Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management. Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months Pulmonary hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug Serious, non-healing wound, ulcer, or bone fracture Uncorrected dehydration Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results Known or suspected allergy to the investigational agent or any agent given in association with this trial Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study Patients unable to swallow oral medications Any malabsorption condition Patients with a hearing impairment (FOR GERMANY ONLY) NSCLC patients with squamous cell carcinoma diagnosis documented either by cytology or biopsy. Excluded therapies and medications, previous and concomitant: Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy for NSCLC Concomitant use of nephrotoxic drugs, ototoxic drugs, anticonvulsant, anti-gout treatment Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section) Radiotherapy during study or within 4 weeks of start of study drug. (Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section) (FOR FRANCE ONLY) Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug (bronchoscopy is allowed) Granulocyte colony stimulating factor (GCSF) or Granulocyte macrophage colony stimulating factor (GMCSF), within 3 weeks of study entry (these growth factors may be used during the study thereafter).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
City
Linz
ZIP/Postal Code
4010
Country
Austria
City
Wien
ZIP/Postal Code
1130
Country
Austria
City
Wien
ZIP/Postal Code
1140
Country
Austria
City
Brasschaat
ZIP/Postal Code
2930
Country
Belgium
City
Bruxelles - Brussel
ZIP/Postal Code
1200
Country
Belgium
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Namur
ZIP/Postal Code
5000
Country
Belgium
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40050410
Country
Brazil
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40170-070
Country
Brazil
City
Salvador
State/Province
Bahia
ZIP/Postal Code
41820 021
Country
Brazil
City
Brasília
State/Province
Distrito Federal
ZIP/Postal Code
70840 901
Country
Brazil
City
Goiania
State/Province
Goiás
ZIP/Postal Code
74605-070
Country
Brazil
City
Goiânia
State/Province
Goiás
ZIP/Postal Code
74075040
Country
Brazil
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30110-090
Country
Brazil
City
Porto Alegre
State/Province
Rio Grande do Sul
ZIP/Postal Code
90050 170
Country
Brazil
City
Porto Alegre
State/Province
Rio Grande do Sul
ZIP/Postal Code
90610-000
Country
Brazil
City
Jaú
State/Province
Sao Paulo
ZIP/Postal Code
17210-120
Country
Brazil
City
Santo Andre
State/Province
Sao Paulo
ZIP/Postal Code
09090-780
Country
Brazil
City
Santo André
State/Province
Sao Paulo
ZIP/Postal Code
09060-870
Country
Brazil
City
Sorocaba
State/Province
Sao Paulo
ZIP/Postal Code
18030-510
Country
Brazil
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
01221020
Country
Brazil
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
01331020
Country
Brazil
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
05403-010
Country
Brazil
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
05651-901
Country
Brazil
City
Rio de Janeiro
ZIP/Postal Code
20231 050
Country
Brazil
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
City
Beijing
ZIP/Postal Code
100021
Country
China
City
Shanghai
ZIP/Postal Code
200030
Country
China
City
Shanghai
ZIP/Postal Code
200433
Country
China
City
Nicosia
ZIP/Postal Code
2006
Country
Cyprus
City
HUS
ZIP/Postal Code
00029
Country
Finland
City
Preitilä
ZIP/Postal Code
21540
Country
Finland
City
Tampere
ZIP/Postal Code
FIN-33521
Country
Finland
City
Bayonne
ZIP/Postal Code
64100
Country
France
City
Grenoble
ZIP/Postal Code
38043
Country
France
City
Grenoble
ZIP/Postal Code
38100
Country
France
City
Hyeres
ZIP/Postal Code
83400
Country
France
City
Le Mans Cedex 2
ZIP/Postal Code
72015
Country
France
City
Marseille
ZIP/Postal Code
13275
Country
France
City
Nantes
ZIP/Postal Code
44805
Country
France
City
Nimes Cedex 2
ZIP/Postal Code
30907
Country
France
City
Paris Cedex 15
ZIP/Postal Code
75908
Country
France
City
Perpignan
ZIP/Postal Code
66000
Country
France
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
City
Strasbourg
ZIP/Postal Code
67901
Country
France
City
Tours
ZIP/Postal Code
37044
Country
France
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69126
Country
Germany
City
Karlsruhe
State/Province
Baden-Württemberg
ZIP/Postal Code
76137
Country
Germany
City
Löwenstein
State/Province
Baden-Württemberg
ZIP/Postal Code
74245
Country
Germany
City
Gauting
State/Province
Bayern
ZIP/Postal Code
82131
Country
Germany
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60431
Country
Germany
City
Hofheim
State/Province
Hessen
ZIP/Postal Code
65719
Country
Germany
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45122
Country
Germany
City
Köln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
51109
Country
Germany
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04207
Country
Germany
City
Großhansdorf
State/Province
Schleswig-Holstein
ZIP/Postal Code
22927
Country
Germany
City
Bad Berka
State/Province
Thüringen
ZIP/Postal Code
99437
Country
Germany
City
Hamburg
ZIP/Postal Code
21075
Country
Germany
City
Heraklion
State/Province
Creta
ZIP/Postal Code
711 10
Country
Greece
City
Athens
ZIP/Postal Code
11527
Country
Greece
City
Budapest
ZIP/Postal Code
1121
Country
Hungary
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
City
Deszk
ZIP/Postal Code
6772
Country
Hungary
City
Matrahaza
ZIP/Postal Code
3233
Country
Hungary
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
City
Torokbalint
ZIP/Postal Code
2045
Country
Hungary
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel
City
Holon
ZIP/Postal Code
58100
Country
Israel
City
Kfar Saba
ZIP/Postal Code
4428164
Country
Israel
City
Rehovot
ZIP/Postal Code
7610001
Country
Israel
City
Tel Hashomer
ZIP/Postal Code
5262000
Country
Israel
City
Rozzano
State/Province
Milano
ZIP/Postal Code
20089
Country
Italy
City
Monza
State/Province
Monza-Brianza
ZIP/Postal Code
20052
Country
Italy
City
Aviano
State/Province
Pordenone
ZIP/Postal Code
33081
Country
Italy
City
Bologna
ZIP/Postal Code
40138
Country
Italy
City
Catania
ZIP/Postal Code
95122
Country
Italy
City
Firenze
ZIP/Postal Code
50134
Country
Italy
City
Livorno
ZIP/Postal Code
57124
Country
Italy
City
Milano
ZIP/Postal Code
20132
Country
Italy
City
Roma
ZIP/Postal Code
00152
Country
Italy
City
Sassari
ZIP/Postal Code
07100
Country
Italy
City
Venezia
ZIP/Postal Code
30122
Country
Italy
City
Verona
ZIP/Postal Code
37134
Country
Italy
City
México
State/Province
Distrito Federal
ZIP/Postal Code
14080
Country
Mexico
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44280
Country
Mexico
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
City
Den Bosch
ZIP/Postal Code
5211 RW
Country
Netherlands
City
Ede
ZIP/Postal Code
6716 RP
Country
Netherlands
City
Harderwijk
ZIP/Postal Code
3844 DG
Country
Netherlands
City
Heerlen
ZIP/Postal Code
6419 PC
Country
Netherlands
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08227
Country
Spain
City
Cruces/Barakaldo
State/Province
Bilbao
ZIP/Postal Code
48903
Country
Spain
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
City
Madrid
ZIP/Postal Code
28040
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Málaga
ZIP/Postal Code
29010
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Valencia
ZIP/Postal Code
46014
Country
Spain
City
Valencia
ZIP/Postal Code
46015
Country
Spain
City
Basel
State/Province
Basel-Stadt
ZIP/Postal Code
4031
Country
Switzerland
City
Genéve
State/Province
Genève
ZIP/Postal Code
1205
Country
Switzerland
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
City
Aberdeen
State/Province
Grampian
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
City
Wolverhampton
State/Province
West Midlands
ZIP/Postal Code
WV10 0QP
Country
United Kingdom
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
22851564
Citation
Paz-Ares LG, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J, Zhang L, Liao M, Sun Y, Gans S, Syrigos K, Le Marie E, Gottfried M, Vansteenkiste J, Alberola V, Strauss UP, Montegriffo E, Ong TJ, Santoro A; NSCLC [non-small-cell lung cancer] Research Experience Utilizing Sorafenib (NExUS) Investigators Study Group. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012 Sep 1;30(25):3084-92. doi: 10.1200/JCO.2011.39.7646. Epub 2012 Jul 30.
Results Reference
result
Links:
URL
http://www.clinicaltrialsregister.eu
Description
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Learn more about this trial

A Phase III Randomized, Double-blind, Placebo Controlled Trial Comparing the Efficacy of Gemcitabine, Cisplatin and Sorafenib to Gemcitabine, Cisplatin and Placebo in First-Line Treatment of Patients With Stage IIIb With Effusion and Stage IV Non-Small Cell Lung Cancer (NSCLC)

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