E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
First-line chemotherapy for patients with metastatic colorectal cancer |
Pazienti con carcinoma colorettale metastatico non pretrattati. |
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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 | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
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 demonstrate, in terms of time to progression (TTP) or death, the non inferiority of each of three bevacizumab-containing chemotherapies. |
Determinare in termini di tempo alla progressione (TTP) o decessi, la non inferiorita` di ciascun dei tre regimi chemioterapici in combinazione con bevacizumab. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate and compare the toxicity and the safety profile of the three bevacizumab-containig chemotherapies; - To evaluate the response rate (RR), duration of response (DR), time to treatment failure (TTF), and overall survival (OS) in patients treated with each of three combinations. |
- Valutare il profilo di tossicita` e di safety dei tre regimi chemioterapici in combinazione con bevacizumab.- Valutare il tasso di risposte obiettive (RR),la durata delle risposte (DR),il tempo al fallimento terapeutico (TTF),e la sopravvivenza globale (OS) dei tre regimi chemioterapici in combinazione con bevacizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven diagnosis of colon or rectum with metastatic disease. 2. Patients must not have previously received systemic treatment for advanced disease. Adjuvant chemotherapy or neo-adjuvant treatment for non-metastatic disease (M0) is allowed if completed at least 6 months prior to initiation of the study treatment. If prior adjuvant therapy was received, patients must not have progressed during therapy or within 6 months of its completation. 3. Age >= 18 4. ECOG Performance Status 0-1 (Appendix I) 5. Life expectancy of at least 12 weeks 6. At least one target lesion with a minimum lesion size as per the RECIST criteria 7. Laboratory requirements: - Neutrophils >=1.5 x 109/L, Platelets >= 100 x 109/L, and Haemoglobin >= 10g/dL - Total bilirubin <= 1.5 time the upper-normal limits (UNL) of the Institutional normal values; ASAT (SGOT) and/or ALAT (SGPT) <= 2.5 x UNL, or <= 5 x UNL in case of liver metastases; alkaline phosphatase <= 2.5 x UNL, <= 5 x UNL in case of liver metastases, <= 10 x UNL in case of bone metastases; LDH <1500 U/L - Creatinine clearance >50 mL/min or serum creatinine <= 1.5 x UNL) - Urine dipstick of proteinuria <2+. Patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <= 1g of protein/24 hr. 8. Written informed consent. 9. Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center. |
1. Pazienti con diagnosi confermata istologicamente o citologicamente di carcinoma colorettale metastatico 2. Pazienti non pretrattati con terapia sistemica per la malattia avanzata. La chemioterapia adiuvante, o neoadiuvante per malattia non metastatica (M0), e` permessa se e` stata completata almeno 6 mesi prima dell?inizio del trattamento. Se e` stata somministrata chemioterapia adiuvante, i pazienti non devono essere andati incontro a progressione durante la terapia o entro 6 mesi dal suo completamento. 3. Eta` >= 18 anni 4. Performance Status ECOG 0-1 5. Attesa di vita di almeno 12 settimane 6. Lesioni misurabili e/o valutabili secondo i criteri RECIST 7. Parametri di Laboratorio: ? Neutrofili >= 1.5 x 109/L e Piastrine >= 100 x 109/L e emoglobina >= 10g/dL ? Bilirubina totale <= 1.5 il limite superiore normale (LSN) del range dei valori normali del Centro e ASAT (SGOT) e/o ALAT (SGPT) <= 2.5 x LSN, o <= 5 x LSN in caso di metastasi epatiche, fosfatasi alcalina <= 2.5 x UNL, <= 5 x LSN in caso di metastasi epatiche, <= 10 x LSN in caso di metastasi ossee. LDH <1500 U/L ? Clearance della Creatinina >50 mL/min o creatinina serica <= 1.5 x LSN) ? Proteinuria (dipstick) <2+. Pazienti con proteinuria >= 2+ al basale, devono sottoporsi a raccolta urine di 24 ore e devono avere <= 1 g di proteine/24 ore. 8. Consenso Informato scritto. 9. Accessibilita` geografica per il trattamento e follow up. Pazienti arruolati in questo studio devono essere trattati e seguiti nel Centro partecipante. |
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E.4 | Principal exclusion criteria |
1. Radiotherapy to any site within 4 weeks before the study. 2. Symptomatic and/or unstable pre-existing brain metastases or leptomeningeal metastases requiring medication. 3. History of inflammatory bowel disease and/or acute/subacute bowel occlusion. 4. Serious non-healing wound or ulcer. 5. Evidence of bleeding diathesis or coagulopathy. 6. Uncontrolled hypertension. 7. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 8. Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants for therapeutic purposes. 9. Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration. 10. Treatment with any investigational drug within 30 days prior to enrolment. 11. Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications 12. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ 13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. 14. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication. 15. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. |
1. Radioterapia nelle precedenti 4 settimane. 2. Metastasi cerebrali sintomatiche e/o instabili o metastasi leptomeningee che richiedono trattamento. 3. Storia di malattia infiammatoria intestinale e/o occlusione intestinale acuta/subacuta. 4. Ulcera o ferita non rimarginata grave. 5. Evidenza di diatesi emorragica o coagulopatia. 6. Ipertensione non controllata. 7. Malattia cardiovascolare clinicamente significativa (attiva): per esempio, accidente cerebrovascolare (≤6 mesi), infarto miocardico (≤6 mesi), angina instabile, insufficienza cardiaca congestizia di grado II o maggiore secondo la New York Heart Association (NYHA), aritmia cardiaca grave che richiede trattamento. 8. Trattamento recente (nei 10 giorni precedenti l?inizio del trattamento) o in corso con anticoagulanti orali o parenterali somministrati a dosaggio pieno a scopo terapeutico. 9. Trattamento cronico, giornaliero, con aspirina ad alte dosi (>325 mg/die) o con altri farmaci che possano predisporre all?ulcera gastroinestinale. 10. Trattamento con qualsiasi farmaco sperimentale nei 30 giorni precedenti l?arruolamento. 11. Pazienti con allergia confermata alle proteine delle cellule ovariche di criceto cinese, o a uno qualsiasi dei componenti dei farmaci dello studio. 12. Altre concomitanti patologie neoplastiche diagnosticate negli ultimi 5 anni con l?eccezione del carcinoma basocellulare e del carcinoma cervicale in situ. 13. Intervento di chirurgia maggiore, biopsia a cielo aperto, o lesione traumatica significativa nei 28 giorni precedenti l?inizio del trattamento, o previsione della necessita` di un intervento di chirurgia maggiore durante il corso dello studio. 14. Assenza di integrita` fisica del tratto gastrointestinale superiore, sindrome da malassorbimento, o inabilita` ad assumere farmaci orali. 15. Donna in gravidanza o in allattamento. Donna senza test di gravidanza o con un test di gravidanza positivo al basale. La donna in postmenopausa e` considerata non fertile se amenorroica da almeno 12 mesi. Donne e maschi sessulamente attivi (o potenzialmente fertili) che non praticano un metodo contraccettivo durante lo studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to disease progression and best response rate. |
Tempo di progressione e migliore tasso di risposta. |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
confronto tra tre diversi regimi chemioterapici |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 51 |
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 | 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
| |
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 |