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)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Sorafenib (Nexavar, BAY43-9006); Placebo; Gemcitabine; Cisplatin
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; Placebo 2 tablets po bid; applied in combination with chemotherapy components: Gemcitabine 1250 mg/m^2 IV, Cisplatin 75 mg/m^2 IV; Chemotherapy component; Gemcitabine 1250 mg/m^2 IV; Chemotherapy component; Cisplatin 75 mg/m^2 IV
Intervention MeSH terms: Gemcitabine; Sorafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 904.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer (NSCLC); Cancer

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)
    

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).