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)

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2008-000662-23-BE
• Date of registration: 04/06/2008
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann La-Roche Ltd
• Public title: 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)
• Scientific title: 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)
• Date of first enrolment: 16/06/2008
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000662-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): Therapeutic use (Phase IV):

Countries of recruitment

Belgium, Czech Republic, Denmark, France, Germany, Hungary, Italy, Netherlands, Spain, United Kingdom

Key inclusion & exclusion 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 < 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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Intervention(s)

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 code: RO-487-6646
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

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 code: RO-487-6646
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Gemzar
Product Name: gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058814
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Gemzar
Product Name: gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058814
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Carboplatin
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CARBOPLATIN
CAS Number: 41575944
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Oncotax or any other brand
Product Name: paclitaxel
Product Code: RO-024-7506
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

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

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

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.

Secondary ID(s)

BO21015

2008-000662-23-NL