E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cáncer de pulmón no microcítico metastásico o recurrente, localmente avanzado
Locally advanced, metastatic or recurrent Non-small Cell Lung Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Roche Sample Repository protcol Version A dated on 14 Feb 2008 Patients who have been enrolled in the study will be asked to participate in the Roche Sample Repository (RSR) project in countries where RSR sampling is to be undertaken. The RSR project involves taking a 9 mL blood sample for pharmacogenetic and genetic research. Taking part in the RSR project is entirely optional and is subject to a separate signed informed consent.
Biomarker sample Repository (BSR) Plasma & Tumor (Included in the protocol study). Patients who have been enrolled in the study will be asked to consent to allow samples collected to be used for additional exploratory biomarker research. No additional sampling is required. |
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E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will formally end once the survival analysis has taken place, or the last patient has completed their last visit (when the last patient has completed the 6-months safety follow-up). Whichever occurs last.
It is anticipated that, after approximately 35 months, the number of patients still receiving study treatment will be low. The trial sponsors will ensure that patients still receiving study treatment at this time can continue study treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |