A randomized, multicenter phase II study to explore whether biomarkers correlate with treatment outcome in chemo-naive patients with advanced or recurrent non-squamous non-small cell lung cancer, who receive treatment with bevacizumab (at a dose of either 7.5 mg/kg or 15 mg/kg) in addition to carboplatin based chemotherapy (gemcitabine or paclitaxel)

Conditions: ocally advanced, metastatic or recurrent Non-small Cell Lung Cancer
MedDRA version: 9.1Level: LLTClassification code 10061873Term: Non-small cell lung cancer

Registration Number: EUCTR2008-000662-23-CZ

Lead Sponsor: F. Hoffmann La-Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

Age 18 years or above
Life expectancy > 12 weeks
Able to comply with the protocol
Histologically or cytologically documented inoperable, locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (stage IV) or recurrent non-squamous NSCLC. Diagnoses of non-squamous NSCLC based on sputum cytology alone are not acceptable. Mixed tumors should be categorized according to the predominant cell type
At least one measurable tumor lesion according to the RECIST criteria
ECOG performance status 0-1
Adequate hematological function: ANC = 1.5 x 109/L; platelets = 100 x 109/L, Hb = 9 g/dL
INR < or = 1.5 (or PT within normal range) and aPTT < or = 1.5 x ULN within 7 days prior to starting study treatment
Adequate liver function: Serum bilirubin < or = 1.5 x ULN; transaminases < or = 2.5 x ULN (in the presence of liver metastases :< 5 x ULN)
Adequate renal function: Creatinine clearance, measured and/or calculated according to the formula of Cockroft and Gault = 50 mL/min AND Urine dipstick for proteinuria < 2+. If urine dipstick is = 2+, 24- hour urine must demonstrate < or = 1 g of protein in 24 hours
Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Prior chemotherapy or treatment with another systemic anti cancer agent (for example monoclonal antibodies, tyrosine kinase inhibitors) NOTE: prior surgery is permitted if the criteria below do not apply:
Surgery (including open biopsy) or significant traumatic injury within the last 4 weeks prior to first dose or anticipation of the need for major surgery during study treatment.
Minor surgical procedures within 2 days prior randomization
Radiotherapy within the 4 weeks prior to the first dose
Patients who have had radiotherapy = 4 weeks prior to the first dose of study treatment, but are experiencing acute toxic effects of radiotherapy
Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component •History of = grade 2 hemoptysis (bright red blood of at least 2.5 mL)
History of peripheral sensory neuropathy of Grade 2 or more
Evidence of CNS metastases, even if previously treated
Evidence of tumor invading or abutting major blood vessels
Pregnant or lactating women
Fertile men or women of childbearing potential not using adequate contraception
Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, DCIS treated surgically with curative intent
Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to starting study treatment
Known hypersensitivity to any of the study drugs
Non-healing wound, ulcer (including peptic ulcer) or bone fracture
History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
Active gastrointestinal bleeding
Uncontrolled hypertension systolic > 150 mmHg and/or diastolic > 100 mmHg
Clinically significant cardiovascular disease to include but not restricted to for example CVA (< or = 6 months before randomization), myocardial infarction (< or = 6 months before randomization), unstable angina, NYHA =grade 2 CHF, arrhythmia uncontrolled by medication
Current or recent (within 10 days of first dose) use of aspirin (> 325 mg/day) clopidogrel > 75 mg/day, or treatment with dipyramidole, ticlopidine, and cliostazol
Current or recent (within 10 days prior to study treatment start) use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (not prophylactic) purposes
Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk of treatment-related conditions
Increased risk of gastrointestinal perforation, hypertension, would healing complications, thromboembolism or hemorrhage (for thromboembolism and hemorrhage risk, this concerns risks other than those related to NSCLC per se)
Active infection requiring iv antibiotics at randomization
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of randomization