E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with UNOPERABLE NON NON SQUAMOUS 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 | 10001160 |
E.1.2 | Term | Adenocarcinoma lung |
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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 |
Assessment of the antitumoral activity and safety profile of three different dosages of Bevacizumab in association to a novel metronomic chemotherapic schedule mPE in terms of objective responses. |
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E.2.2 | Secondary objectives of the trial |
Assessment of time to progression and overall survival. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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. Age ≥ 18 years ECOG performance status 0-3 Life expectancy > 12 weeks Adequate hematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL INR ≤1.5 and PTT ≤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 case of liver metastatases <5 x ULN) Adequate renal function: o Creatinine clearance, measured and calculated according to the formula of Cockroft and Gault ≥ 50 ml/min, and o Urine dipstick for proteinuria <2+. If urine dipstick is ≥2+, 24 hour urine must demonstrate ≤ 1g of protein in 24 hours Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women Head CT or MRI imaging with and without infusion of contrast material in patients who have signs and symptoms of CNS disease Prior neoadjuvant/adjuvant chemotherapy or radiation therapy is allowed as long as the last dose was not within 6 months prior to randomization. Written informed consent |
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E.4 | Principal exclusion criteria |
Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component History of hemoptysis, defined as bright red blood of at least half a teaspoon Brain metastases or spinal cord compression (CT or MRI of the head is required in symptomatic patients within 4 weeks prior to randomization) Evidence of tumor invading or abutting major blood vessels Surgery (including open biopsy), significant traumatic injury or radiotherapy within the last 4 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment Pregnant or lactating women Fertile men or women 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 or bone fracture History of thrombotic hemorrhagic disorders Uncontrolled hypertension Clinically significant cardiovascular disease for example CVA (≤6 months before randomization), myocardial infarction (≤6 months before randomization), unstable angina, NYHA ≥ grade 2 CHF, arrhythmia requiring medication Current or recent (within 10 days of first dose of study treatment) use of aspirin (> 325mg/day) or other NSAID with anti-platelet activity or treatment with dipyramidole, ticlopidine, clopidogrel and cilostazol Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Assessment of the antitumoral activity and safety profile of three different dosages of Bevacizumab in association to a novel metronomic chemotherapic schedule mPE in terms of objective responses. Assessment of time to progression and overall survival. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
| |
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 | 0 |
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 | 0 |