E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with stage IIIb/IV non-small cell lung cancer |
Trattamento di pazienti con NSCLC allo stadio IIIb-IV |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To evaluate the objective response rate (Complete Response (CR) and Partial Response (PR)) by modified RECIST for AMG 951 at varying dose schedules in combination with carboplatin / paclitaxel ± bevacizumab for subjects with NSCLC. |
Valutare, secondo i criteri RECIST modificati, il tasso di risposte obiettive (risposte complete e risposte parziali) ad AMG 951 somministrato a diverse posologie in combinazione con carboplatino/paclitaxel ± bevacizumab in soggetti con NSCLC. |
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E.2.2 | Secondary objectives of the trial |
To evaluate overall response rate (CR, PR and Stable Disease (SD)), progression-free survival (PFS), time to response, duration of response, time to progression (TTP) and overall survival for AMG 951 at varying dose schedules. To evaluate the safety profile of AMG 951 at varying dose schedules. To evaluate the formation of anti-AMG 951 antibodies. To characterize the pharmacokinetics of AMG 951 |
Valutare il tasso globale di risposta,la sopravvivenza libera da progressione,il tempo alla risposta,la durata della risposta,il tempo alla progressione e la sopravvivenza globale con AMG 951 somministrato a diverse posologie.Valutare il profilo di sicurezza di AMG 951 somministrato a diverse posologie.Valutare la formazione di anticorpi anti-AMG 951.Caratterizzare la farmacocinetica di AMG 951. |
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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 |
PHARMACOGENETIC: Vers: Date: Title: Objectives:
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FARMACOGENETICA: Vers: Data: Titolo: Obiettivi:
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E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC). Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy. • Subjects must have advanced NSCLC defined as stage IIIb with malignant pleural effusion or Stage IV or recurrent disease. Subjects with non-measurable but evaluable disease can be included in the phase 1b study, but disease must be measurable to be included in the phase 2 study • Planning to receive up to 6 cycles of chemotherapy • ECOG performance status of 0 or 1 • Life expectancy greater than 3 months • `¥ 18 years old • Subjects must sign and date a written Independent Ethics Committee (IEC)-approved Informed Consent Form • International Normalization Ratio (INR) `¤ 1.2 and PTT `¤ ULN within 1 week prior to enrollment |
NSCLC documentato istologicamente o citologicamente. I tumori misti devono essere classificati secondo la popolazione cellulare predominante a meno che siano presenti elementi a piccole cellule, che rendono il soggetto ineleggibile. La valutazione istologica o citologica puo` essere fatta su biopsie o aspirati effettuati su metastasi tumorali • Carcinoma polmonare non microcitoma avanzato allo stadio IIIB con effusione pleurica di origine maligna oppure allo stadio IV oppure recidivato. Nella fase 1b possono essere arruolati soggetti con malattia non misurabile ma valutabile, mentre nella fase 2 possono essere arruolati solo soggetti con malattia misurabile • Soggetto che ha in programma di ricevere fino a 6 cicli di chemioterapia • Performance status ECOG pari a 0 o 1 • Attesa di vita pari o superiore a 3 mesi • Soggetto di eta` pari o superiore a 18 anni • Il soggetto deve firmare e datare un modulo di consenso informato scritto precedentemente approvato dal Comitato Etico • International Normalization Ratio (INR) `¤ 1,2 e PTT `¤ al limite superiore dei valori normali di laboratorio (ULN) entro 1 settimana precedente l`arruolamento |
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E.4 | Principal exclusion criteria |
Prior malignancy other than NSCLC (except in situ basal cell carcinoma or in situ cervical cancer), unless have been treated with curative intent with no evidence of disease for `¥ 3 years • Untreated or unstable central nervous system (CNS) metastases. Subjects with CNS metastases that are both definitively treated and stably controlled are eligible for cohorts A and B of the phase 2 part of the study if all of the following apply: 1) definitive therapy has been administered (surgery and/or radiation therapy); 2) there is no additional treatment planned for brain metastases; 3) the subject is clinically stable; 4) the subject is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment • Myocardial infarction, or unstable or uncontrolled disease or condition related to or impacting cardiac function (eg, unstable angina, congestive heart failure [New York Heart Association > class II]) within 1 year of enrollment • Uncontrolled hypertension defined as: systolic blood pressure `¥ 150 mm Hg OR diastolic blood pressure `¥ 100 mm Hg (antihypertensive therapy to achieve these parameters is allowable) • History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders within 1 year of enrollment - Recent major surgical procedure within 28 days prior to enrollment or not yet recovered from prior major surgery (For the full list see protocol.) |
Precedente neoplasia diversa dal NSCLC (escluso basalioma in situ o carcinoma della cervice in situ), a meno che trattata con intento curativo, e senza alcuna evidenza di malattia per almeno 3 anni • Metastasi del SNC non trattate o non controllate. I soggetti con metastasi del SNC sia trattate in modo definitivo che stabilmente controllate sono eleggibili per l`arruolamento nelle sole coorti A e B della fase 2 dello studio, se tutte le seguenti condizioni sono soddisfatte: 1) hanno ricevuto una terapia (terapia chirurgica e/o radiante) considerata definitiva; 2) non e` previsto alcun trattamento aggiuntivo per tali metastasi; 3) il soggetto e` clinicamente stabile; 4) non sta ricevendo corticosteroidi oppure riceve una dose di corticosteroidi stabile da almeno 2 settimane prima dell`arruolamento. • Soggetti con NSCLC squamocellulare (tranne per le sole coorti A e Bdella fase 2 dello studio) • Storia di infarto miocardico o di altre patologie non stabili o non controllate che possano influenzare la funzione cardiaca (ad es. angina instabile, insufficienza cardiaca congestizia di classe NYHA > 2) entro l`anno precedente l`arruolamento • Ipertensione non controllata definita come pressione sistolica > 150 mmHg OPPURE pressione diastolica > 100 mmHg (e` permessa l`assunzione di terapie antiipertensive per ottenere i valori richiesti dallo studio) • Storia di trombosi arteriosa, embolia polmonare, trombosi venosa profonda o patologie emorragiche entro un anno precedente l`arruolamento • Soggetti che hanno subito un`importante intervento chirurgico nei 28 giorni precedenti l`arruolamento o soggetti non ancora dimessi da un precedente importante intervento chirurgico.(Per l`elenco completo si vedano protocollo e sinossi.) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (complete or partial response) |
Tasso di risposte obiettive (risposte complete o parziali) |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
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) | 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.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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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End of study will be defined as the date when the last subject completes the safety follow up visit (approximately 4 weeks after the final dose of protocol specified therapy). |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |