Locally advanced, metastatic or recurrent Non-small Cell Lung Cancer MedDRA version: 9.1 Level: LLT Classification code 10061873 Term: Non-small cell lung cancer
Conditions
Interventions
Trade Name: Avastin
Product Name: bevacizumab
Product Code: RO-487-6646
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: bevacizumab
CAS Number: 216974
Current Sponsor c
Sponsors
F. Hoffmann La-Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 ( 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Explore the correlation of biomarkers with response rate as assessed by the investigator (according to RECIST) in patients treated with carboplatin based chemotherapy in combination with 7.5 mg/kg or 15 mg/kg of bevacizumab;Secondary Objective: Secondary: To evaluate PFS in patients treated with carboplatin based chemotherapy in combination with bevacizumab To evaluate response rate, disease control rate and duration of response (RECIST) To evaluate Overall Survival To evaluate the safety profile Exploratory: Explore changes in biomarkers Explore the correlation of biomarkers with response rate as assigned by the independent radiological review (according to RECIST criteria) Explore the correlation of response rate according to RECIST with tumor volume changes as assessed by HRCT To evaluate whether genetic variants of VEGF A and VEGF receptors affect pharmacodynamic/efficacy/safety parameters To explore the relationship between bevacizumab exposure and biomarkers ;Primary end point(s): Exploration of the correlation of biomarkers with response rate as assessed by the investigator (according to RECIST) in patients treated with carboplatin based chemotherapy in combination with 7.5 mg/kg or 15 mg/kg of bevacizumab. Primary parameters are the levels of the biomarker the primary biomarkers at baseline. | — |
Countries
Belgium, Czech Republic, Denmark, France, Germany, Hungary, Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed