E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Colo-Rectal Cancer |
Cancro al Colon-Retto metastatico |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Colo-Rectal Cancer |
Cancro al Colon-Retto metastatico |
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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 | 21.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
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 assess progression free survival associated with the study treatment focusing on its relationship with baseline serum levels of IL-8. |
Valutare la Sopravvivenza libera da progressione (PFS) associata al trattamento in studio concentrandosi sulla sua correlazione con i livelli sierici basali di IL-8. |
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E.2.2 | Secondary objectives of the trial |
To assess: Radiologic Response Rate (rRR), Overall Survival (OS), safety profile, associated with the study treatment and their relationship with baseline levels of IL-8 |
Valutare: Tasso di Risposta Radiologica (rRR), sopravvivenza globale (OS), profilo di sicurezza, associati al trattamento in studio e la loro correlazione con i livelli sierici basali di IL-8. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult age (>= 18 years old); 2. An Eastern Cooperative Oncology Group (ECOG); performance status (PS) of 0 or 1; 3. Histologically or cytologically proven colorectal adenocarcinoma with metastatic disease not menable to potentially curative treatment; 4. Measurable disease according to the RECIST criteria 1.1; 5. Documented progression while on or after completion of a single prior oxaliplatin-containing regimen in patients treated in the neoadjuvant and metastatic setting; documented relapsing disease within 6 months of completion of oxaliplatinbased regimen in patients treated in the adjuvant setting; 6. Aflibercept in combination with irinotecan planned as per standard clinical practice and decision by the treating oncologist; 7. Any adverse events from prior anticancer therapy must have recovered to grade = 1 ([NCI-CTCAE] version 5.0) before study enrolment; 8. Patients were to have adequate bone marrow, liver and renal: alanine transaminase (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases], total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases], neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L, proteinuria ¿ 1+ on the dipstick, creatinine = 2.5 x institutional ULN or creatinine clearance of =40 mL/min; 9. Signed written consent form; 10. Patients of reproductive potential, must use adequate contraception methods; |
1-Età adulta (>= 18 anni); 2-ECOG performance status di 0 o 1; 3-conferma istologica o citologica di adenocarcinoma colorettale, con malattia metastatica non suscettibile ad un trattamento potenzialmente curativo; 4-Malattia misurabile in accordo ai criteri RECIST 1.1.; 5-Documentata progressione di malattia durante o dopo il completamento di un singolo regime precedente contenente oxaliplatino in pazienti trattati nel setting neoadiuvante e metastatico;documentata malattia recidiva entro 6 mesi dal completamento del regime basato su oxaliplatino in pazienti trattati nel setting adiuvante; 6-Aflibercept in combinazione con irinotecano pianificato come da pratica clinica e su decisione del medico oncologo; 7-Eventuali Eventi avversi derivanti da precedenti terapie antineoplastiche devono essere recuperate al grado = 1 ([NCI-CTCAE] versione 5.0 )prima dell’arruolamento; 8-Pazienti con adeguata funzionalità al midollo osseo, al fegato e renale: alanina transaminasi (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presenza di metastasi epatiche], bilirubina totale = 1.5 × institutional ULN [= 2.0 x ULN in presenza di metastasi epatiche], conta di neutrofili = 1.5 x 109/L, conta di piastrine = 100 x 109/L, proteinuria ¿ 1+ al dipstick, creatinina = 2.5 x institutional ULN o clearance della creatinina =40 mL/min.; 9- Consenso informato scritto; 10- Pazienti con potenziale riproduttivo, devono usare adeguati metodi contraccettivi; |
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E.4 | Principal exclusion criteria |
1. Radiation therapy or any previous anti-neoplastic systemic treatment within the past 28 days before study enrollment; 2. History of major surgery within 28 days before study enrollment; 3. Known prior malignancies or known brain metastases ( patients with adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or any other cancer from which the patient had been disease-free for more than 10 years are permitted); 4. Severe acute or chronic medical condition that may impair the ability to participate in the study or may interfere with the interpretation of results; 5. Any contraindication to the administration of aflibercept, irinotecan, 5-fluorouracil or folinic acid; 6. History of any auto-immune or rheumatic disease; any active bacterial or viral infection; 7. History of uncontrolled hypertension and diabetes within 3 months before enrollment; 8. History of daily use of corticosteroids or immune-suppressive medications; 9. Deep vein thrombosis within 4 weeks before treatment; 10. Pregnant and breast-feeding women; 11. Patients of reproductive potential who refuse to use effective methods of contraception; |
1. Radioterapia o qualsiasi precedente trattamento sistemico anti-neoplastico negli ultimi 28 giorni precedenti l’arruolamento; 2. Storia di chirurgia maggiore entro 28 giorni precedenti l’arruolamento; 3. Note neoplasie precedenti o metastasi al cervello (sono invece ammessi pazienti con cancro a cellule basali o a cellule squamose adeguatamente trattati, con carcinoma in situ della cervice o qualsiasi altro tumore da cui il paziente risulta libero da malattia da più di 10 anni). 4. Condizione medica severa acuta o cronica che può compromettere la capacità di partecipare allo studio o può interferire con l'interpretazione dei risultati; 5. Qualsiasi controindicazione alla somministrazione di aflibercept, irinotecano, 5-fluorouracile o acido folinico; 6. Storia di qualsiasi malattia autoimmune o reumatica; qualsiasi infezione batterica o virale attiva; 7. Storia di ipertensione incontrollata e diabete nei 3 mesi precedenti l’arruolamento; 8. Storia dell'uso quotidiano di corticosteroidi o farmaci immunosoppressori; 9. Trombosi venosa profonda entro le 4 settimane precedenti il trattamento; 10. Donne in stato di gravidanza e allattamento; 11. Pazienti in età riproduttiva che rifiutano di utilizzare metodi efficaci di contraccezione; |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point of the study is progression free survival (PFS), with the objective to estimate the difference in PFS between the two groups defined on the basis of their baseline IL-8 levels (>= vs. < than median). |
L’Endpoint primario dello studio è la Sopravvivenza libera da progressione (PFS), con l'obiettivo di stimare la differenza in PFS tra i due gruppi definiti sulla base dei loro livelli di IL-8 al basale (>= VS. < della mediana) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of the study are: • Radiologic Response Rate (rRR) • Overall Survival (OS) • Safety profile |
Gli end point secondari dello studio sono: - Tasso di Risposta Radiologica (rRR) - Sopravvivenza globale (OS) - Profilo di sicurezza |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
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 |
To assess progression free survival associated with the study treatment and its relationship with baseline serum levels of IL-8. |
Valutare la Sopravvivenza libera da progressione (PFS) associata al trattamento in studio e la sua correlazione con i livelli sierici basali di IL-8. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 15 |
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
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Exstimed LVLS December 2020 |
LVLS stimata Dicembre 2020 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |