| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Primera línea para el cáncer de pulmón no microcítico avanzado (estadios IIIb y IV)
Advanced Non-Small-Cell-Lung-Cancer (Stage IIIb and IV) 1st line
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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 | 10029521 |
| E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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| 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 | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
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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 |
| Estimate the hazard ratio for progression free survival (PFS) duration in patients with previously untreated advanced stage NSCLC for the combination of erlotinib plus bevacizumab relative to the combination of standard platinum based chemotherapy plus bevacizumab. |
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| E.2.2 | Secondary objectives of the trial |
•To evaluate the safety profile of erlotinib in combination with bevacizumab relative to the combination of standard chemotherapy and bevacizumab in the treatment of NSCLC patients.
•To estimate the effect of adding erlotinib to bevacizumab as compared to the combination of standard platinum based chemotherapy plus bevacizumab on OS, objective RR, DCR and duration of response and disease control.
•To explore changes in QoL in the two treatment arms
•To investigate the effect of the combination of erlotinib plus bevacizumab on subgroups such as patients with EGFR protein expression positive tumors measured by IHC, patients with EGFR gene amplified tumors measured by FISH, and patients with tumors carrying mutations in the EGFR gene in comparison to the combination of standard platinum based chemotherapy plus bevacizumab.
•To perform exploratory evaluations of tumor and normal tissue for biological and genomic determinants involved in the EGFR and VEGF pathway. |
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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 |
Proyecto de investigación del banco de muestras de Roche en asociación con el protocolo BO20571. Estudio de fase II de Tarceva® en combinación con Avastin® frente a quimioterapia más Avastin® en el tratamiento de primera línea de pacientes con CPNM avanzado.
Version A del 16 de marzo de 2007
Roche Sample Repository Research Project in association with protocol BO20571 A Phase II study of Tarceva® in Combination with Avastin® versus chemotherapy plus Avastin® in 1st line advanced NSCLC patients.
Objectives: To obtain a single blood sample from consenting patients enrolled in associated study BO20571 for pharmacogenetic and genetic research analysis. |
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| E.3 | Principal inclusion criteria |
• Age ≥18 years
• Able to comply with the protocol
• Patients must be able to take oral medication
• Histologically documented inoperable, locally advanced (stage IIIb with supra-clavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (stage IV) or recurrent NSCLC (NOTE: Sputum cytology alone is not acceptable). Tumors with mixed histology should be categorized according to the predominant cell type.
• Formalin fixed paraffin embedded tumor tissue samples representative of the disease must be available for shipment to Roche
• Measurable disease according to RECIST
• ECOG performance status 0-1
• Life expectancy > 12 weeks
• Adequate hematological function : ANC ≥1.5 x 10^9/L; platelets ≥100
x 10^9/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 metastases <5 x ULN)
• Adequate renal function: Creatinine clearance, measured and/or calculated according to the formula of Cockroft and Gault ≥60 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
• Normal serum calcium
• Negative 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 |
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| E.4 | Principal exclusion criteria |
•Squamous non-small cell tumors with central pulmonary lesion (a central lung lesion is defined as any lesion meeting the following criteria epicenter of the tumor is > 2 cm from the costal or diaphragmatic pleura in a 3-dimensional orientation based on each lobe of the lung).
•History of ≥ grade 2 hemoptysis (bright red blood of at least ½ teaspoon).
•Evidence of CNS metastases, even if previously treated. If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases.
•Evidence of tumor invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumor that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary artery or superior vena cava).
•Prior treatment with an investigational or marketed agent that acts either by EGFR inhibition or anti-angiogenesis mechanism. EGFR inhibitors include (but are not limited to) erlotinib, gefitinib, cetuximab, CI-1033 or other anti-EGFR or EGF monoclonal antibody therapy. Angiogenesis inhibitors include (but are not limited to) bevacizumab, thalidomide, CP-547632, sunitinib, and sorafenib.
•Prior chemotherapy or treatment with another systemic anti-cancer agent NOTE: prior surgery and irradiation is permitted (as specified below):
a) Radiotherapy within the last 4 weeks prior to first dose of study treatment. Palliative radiotherapy for bone lesions outside the thoracic region within 2 weeks prior to the first dose of study treatment.
b) 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.
•Any known significant ophthalmologic abnormalities of the surface of the eye (The use of contact lenses is not recommended).
•Lactating women.
•Fertile men or woman of childbearing potential not using effective methods to prevent pregnancy (e.g. 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.
•Known hypersensitivity to any of the study drugs or their excipients.
•Any disease (including psychotic disorders, drug abuse, active infection, 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, hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical 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 for treatment-related complications.
•History of evidence of inherited bleeding diathesis of coagulopathy with the risk of bleeding.
•Non-healing wound, ulcer, or bone fracture, patients with esophageal varices.
•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, including coumadin or warfarin.
•Current or recent (within 10 days of first dose of study treatment) use of acetylic salicylic acid (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel and cilostazol.
•Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to starting study treatment.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) assessed according to the RECIST criteria.
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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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| 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 | 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
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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 | 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 |
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