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) - ND

• Register: EUCTR
• Last refreshed on: 5 November 2012
• Main ID: EUCTR2008-000662-23-IT
• Date of registration: 23/07/2008
• Prospective Registration: Yes
• Primary sponsor: ROCHE
• 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) - ND
• 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) - ND
• Date of first enrolment: 27/02/2009
• 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: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion criteria:
Age ≥ 18 years Life expectancy > 12 weeks Able to comply with the protocol Histologically or cytologically documented inoperable, locally advanced (stage IIIb with supraclavicular lymphnode 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 ≤ 1.5 (or PT within normal range) and aPTT ≤ 1.5 x ULN within 7 days prior to starting study treatment Adequate liver function: Serum bilirubin ≤ 1.5 x ULN; transaminases ≤ 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 ≤ 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 Written informed consent
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 of study treatment or anticipation of the need for major surgery during study treatment. Minor surgical procedures within 2 days prior randomization (including CVAD placement for chemotherapy. Radiotherapy within the last 4 weeks prior to the first dose of study treatment Patients who have had radiotherapy ≥ 4 weeks prior to the first dose of study treatment, but who are still 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. If suspected, the patient should have a CT or MRI scan of the appropriate area within 28 days prior to randomization. Evidence of tumor invading or abutting major blood vessels Pregnant or lactating women Fertile men or woman of childbearing potential not using adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) 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 ...contd


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

Health Condition(s) or Problem(s) studied

Locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic or recurrent non-squamous non-small cell lung cancer
MedDRA version: 9.1 Level: LLT Classification code 10061873 Term: Non-small cell lung cancer
MedDRA version: 9.1 Level: LLT Classification code 10029515 Term: Non-small cell lung cancer recurrent
MedDRA version: 9.1 Level: LLT Classification code 10059515 Term: Non-small cell lung cancer metastatic

Intervention(s)

Trade Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Gemzar
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Gemcitabine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Gemzar
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Gemcitabine
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

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

Trade Name: Oncotax
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

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: To evaluate progression free survival in patients treated with carboplatin based chemotherapy in combination with 7.5 mg/kg or 15 mg/kg of bevacizumab To evaluate response rate, disease control rate and duration of response (RECIST) in patients treated with carboplatin based chemotherapy in combination with 7.5 mg/kg or 15 mg/kg of bevacizumab To evaluate overall survival in patients treated with carboplatin based chemotherapy in combination with 7.5 mg/kg or 15 mg/kg of bevacizumab To evaluate and assess the safety profile in patients treated with carboplatin based chemotherapy in combination with 7.5 mg/kg or 15 mg/kg of bevacizumab

Primary end point(s): To 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 parameters are the levels of the biomarker the primary biomarkers at baseline.

Secondary ID(s)

BO21015

2008-000662-23-NL