E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced colorectal carcinoma with wild type RAS and FcyRIIIA-V / V |
carcinoma del colon-retto avanzato con RAS wild type e FcyRIIIA-V/V |
|
E.1.1.1 | Medical condition in easily understood language |
advanced colorectal carcinoma / V |
carcinoma del colon-retto avanzato |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Main objective: The aim of the present study is to evaluate the activity of the Cetuximab, Irinotecan and Fluorouracil association in patients with metastatic colorectal cancer selected through the study of RAS and of the genetic polymorphism of the FcγRIIIa V / V |
Obiettivo principale: Lo scopo del presente studio è valutare l’attività dell’associazione Cetuximab, Irinotecan e Fluorouracile in pazienti affetti da cancro del colon-retto metastatico selezionati attraverso lo studio del RAS e del polimorfismo genetico dell’FcγRIIIa V/V |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives: Describe the duration of the response, the progression-free survival (Progression-Free Survival, PFS) and survival (Overall Survival, OS). Evaluate the presence of M1 / M2 macrophages in the tumor microenvironment and correlate it with the response to therapy. Evaluate the toxicity that will be measured with the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
Obiettivi secondari: Descrivere la durata della risposta, la sopravvivenza libera da progressione (Progressione-Free Survival, PFS) e la sopravvivenza (Overall Survival, OS). Valutare la presenza di macrofagi M1/M2 nel microambiente tumorale e correlarla con la risposta alla terapia. Valutare la tossicità che sarà misurata con Common Terminology Criteria for Adverse Events (CTCAE) versione 3.0. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Cytological or histological diagnosis of colorectal adenocarcinoma • wild-type RAS • FcγRIIIa-158V / V genotype • Stage IV • Negative pregnancy test where applicable • Age <75 years • At least 1 lesion measurable according to the RECIST criteria v1.1 • ECOG Performance Status 0 or 1 • Life expectancy> 3 months • Written informed consent |
• Diagnosi citologica o istologica di adenocarcinoma del colon-retto • RAS wild-type • Genotipo FcγRIIIa-158V/V • Stadio IV • Test di gravidanza negativo ove applicabile • Età < 75 anni • Almeno 1 lesione misurabile secondo i criteri RECIST v1.1 • Performance Status ECOG 0 o 1 • Aspettativa di vita >3 mesi • Consenso informato scritto
|
|
E.4 | Principal exclusion criteria |
• Previous systemic anti-tumor treatment; allowed treatment with Capecitabine or fluorouraciol and radiotherapy in the neoadjuvant setting of rectal tumors with therapy terminated for at least 6 months. • Presence of primary non-treated stenosing colorectal neoplasm with endoprosthesis positioning • Neutrophils <2000 / mm³ or platelets <100,000 / mm³ or hemoglobin <9 g / dl • Creatinineemia> 1.5 times the maximum normal value • GOT and / or GPT> 5 times the maximum normal value and / or bilirubinemia> 3 times the maximum normal value • Previous malignant neoplasm (excluding basal or spinocellular cutaneous carcinoma or in situ carcinoma of the uterine cervix) • Infection in active or uncontrolled phase • Other concomitant disorders that are decompensated or uncontrolled or that contraindicate the study drugs at the judgment of the clinician • Presence of brain metastases • Refusal or inability to provide informed consent • Impossibility to guarantee follow-up |
• Precedente trattamento anti-tumorale sistemico; consentito trattamento con Capecitabina o fluorouraciule e radioterapia nel setting neoadiuvante dei tumori del retto con terapia terminata da almeno 6 mesi. • Presenza di neoplasia primitiva del colon-retto stenosante non trattata con posizionamento di endoprotesi • Neutrofili < 2000/mm³ o piastrine < 100.000/mm³ o emoglobina < 9 g/dl • Creatininemia > 1.5 volte il valore massimo normale • GOT e/o GPT >5 volte il valore massimo normale e/o bilirubinemia >3 volte il valore massimo normale • Precedente neoplasia maligna (escluso il carcinoma cutaneo baso o spinocellulare o il carcinoma in situ della cervice uterina) • Infezione in fase attiva o non controllata • Altre patologie concomitanti scompensate o non controllate o che controindicano i farmaci in studio a giudizio del clinico • Presenza di metastasi cerebrali • Rifiuto o incapacità a fornire un consenso informato • Impossibilità a garantire il follow-up
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate if the administration of FOLFIRI / Cetuximab is active in the treatment of the 1st line of patients with metastatic colorectal cancer RAS wt and FcγRIIIA V / V. The answer will be evaluated with the RECIST v1.1. |
Valutare se la somministrazione di FOLFIRI/Cetuximab è attiva nel trattamento di I° linea di pazienti affetti da cancro del colon-retto metastatico RAS wt e FcγRIIIA V/V. La risposta sarà valutata con i RECIST v1.1. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation of the response after 3 months of therapy and thereafter every 3 months until progression. |
Valutazione della risposta dopo 3 mesi di terapia e successivamente ogni 3 mesi fino a progressione. |
|
E.5.2 | Secondary end point(s) |
Describe the duration of the response, progression-free survival (Progression-Free Survival, PFS) and survival (Overall Survival, OS). Evaluate the presence of M1 / M2 macrophages in the tumor microenvironment and correlate it with the response to therapy. Evaluate the toxicity that will be measured with the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
Descrivere la durata della risposta, la sopravvivenza libera da progressione (Progressione-Free Survival, PFS) e la sopravvivenza (Overall Survival, OS). Valutare la presenza di macrofagi M1/M2 nel microambiente tumorale e correlarla con la risposta alla terapia. Valutare la tossicità che sarà misurata con Common Terminology Criteria for Adverse Events (CTCAE) versione 3.0. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation of the response after 3 months of therapy and thereafter every 3 months until progression. |
Valutazione della risposta dopo 3 mesi di terapia e successivamente ogni 3 mesi fino a progressione. |
|
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 | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
Superiority study |
Studio di superiorità |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |