E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastric Cancer |
Carcinoma gastrico |
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E.1.1.1 | Medical condition in easily understood language |
Tumor of the stomach |
Tumore dello stomaco |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001150 |
E.1.2 | Term | Adenocarcinoma gastric |
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 pCR rate of a new chemotherapy regimen (modified FOLFOXIRI) for operable castric cancer using sodium folinate instead of calcium folinate |
Valutare il tasso di risposte patologiche complete (pCR) di un nuovo schema chemioterapico a base di 5-fluororuracile, oxaliplatino ed irinotecan (FOLFOXIRI modificato) per i carcinomi dello stomaco operabili utilizzando il sodio levofolinato in sostituzione del calcio levofolinato, comunemente utilizzato |
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E.2.2 | Secondary objectives of the trial |
- To evaluate additional efficacy parameters; - To evaluatesurvival relapse free survival at 1 year after surgery; - To evaluate the effect of the treatment on patients' quality of life; -To evaluate the safety and tolerability of the perioperative regimen. |
- Valutare ulteriori parametri di efficacia; - Valutare la sopravvivenza libera da ricadute ad un anno dall'intervento chirurgico; - Valutare l'impatto del trattamento sulla qualit¿ della vita dei pazienti; - Valutare la tollerabilit¿ e il profilo di sicurezza del trattamento prioperatorio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females = 18 years old; 2. Written, signed consent for trial participation; 3. Patients should consent to optional provision of a sample of blood (30 ml) and urine (10 ml) at basal time and every month during neoadjuvant, before surgery, one month after surgery, at the end of adjuvant treatment and every 4 months during follow-up (in order that specific correlative marker assays could be performed); 4. Patients should also consent to optional provision of available histological tissue (e.g. bioptic and surgical tissue) in order that correlative marker assays could be performed; 5. Histological or cytological diagnosis of GC; 6. Clinical staging of GC cT2-4/cN-any/cM0 or cT-any/cN+/cM0 (according to the 8th edition of the UICC TNM classification performed with thoraco-abdominal CT scan, ecoendoscopy and esophagogastroduodenoscopy performed within 4 weeks prior to randomization; 7. No prior treatments (chemo or radiotherapy); 8. Measurable disease, defined in accordance with RECIST (Response Evaluation Criteria in Solid Tumors) criteria version 1.1, evaluated with ecoendoscopy, esophagogastroduodenoscopy and thoraco-abdominal CT scan; 9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; 10. Adequate organ function assessed within 4 weeks prior to randomization including: a. Hematologic: absolute neutrophil count (ANC) = 1.5 x 109/L, platelets = 100 x 109/L, haemoglobin = 9.0 g/dL; b. Hepatic: bilirubin = 1.5 times upper limits of normal (ULN), alanine transaminase (ALT) = 3 times ULN; c. Renal: Serum creatinine =1.5 times ULN.
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1. Maschi o femmine di età = 18 anni; 2. Consenso informato scritto prima dell’esecuzione di qualsiasi procedura di protocollo; 3. I pazienti dovrebbero acconsentire alla fornitura opzionale di un campione di sangue (30 ml) e urine (10 ml) al basale, ogni mese durante la terapia neoadiuvante, prima della chirurgia, un mese dopo la chirurgia, al termine della terapia adiuvante ed ogni 4 mesi durante il follow-up; 4. I pazienti dovrebbero acconsentire alla fornitura opzionale del tessuto istologico disponibile (per esempio bioptico e chirurgico); 5. Diagnosi istologica o citologica di carcinoma gastrico; 6. Stadio clinico di carcinoma gastrico cT2-4/cN-/cM0 or cT (qualsiasi)/cN+/cM0 (in accordo all’ottava edizione della classificazione UICC TNM) ottenuto con l’esecuzione di TAC torace-addome, ecoendoscopia ed esofagogastroduodenoscopia eseguita entro le quattro settimane precedenti alla randomizzazione; 7. Nessun trattamento precedente (chemio o radioterapia); 8. Malattia misurabile per criteri RECIST (Response Evaluation Criteria in Solid Tumors) versione 1.1 (Eisenhower et al. 2009), valutata con TAC torace-addome ed ecoendoscopia; 9. Performance status (PS) ECOG di 0 o 1; 10. Adeguata funzionalità d’organo nelle quattro settimane precedenti la randomizzazione e comprendenti i seguenti parametri: a. Ematologici: conta assoluta dei neutrofili (ANC) = 1.5 x 109/L, piastrine = 100 x 109/L, emoglobina = 9.0 g/dL; b. Epatici: bilirubina = 1.5 valori superiori di norma (ULN), alanina amino-transferasi (ALT) = 3 volte ULN; c. Renali: creatinina sierica =1.5 volte ULN.
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E.4 | Principal exclusion criteria |
1. ECOG PS > 1; 2. Metastatic Gastric Cancer; 3. Previous chemo or radiotherapy; 4. Current active infection; 5. Serious pre-existing medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris, or a clinically significant history of cardiac disease or renal disease, neurological disease or condition of peripheral neuropathy); 6. Females who are pregnant or lactating; 7. Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 3 years; 8. Patients unable to undergo medical test for geographical, social or psychological reason; 9. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
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1. ECOG PS > 1; 2. Carcinoma gastrico metastatico; 3. Chemio o radioterapia precedente; 4. Infezione attiva; 5. Condizioni mediche pre-esistenti severe o disordini sistemici concomitanti e severi che potrebbero compromettere la sicurezza del paziente e la sua capacità di terminare lo studio, a discrezione dello sperimentatore (esempio: angina pectoris instabile, storia clinica significativa di malattia cardiaca o renale, malattia neurologica o neuropatia periferica); 6. Donne in gravidanza o allattamento; 7. Pazienti con storia di neoplasia eccetto: tumore della pelle adeguatamente trattato, tumore della cervice adeguatamente curato ed in sede, altri tumori solidi curati e non recidivati da un periodo di tempo > 3 anni; 8. Pazienti non in grado di eseguire i test medici richiesti per ragioni geografiche, sociali o psicologiche; 9. Noto deficit di diidropirimidina deidrogenasi (DPD).
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E.5 End points |
E.5.1 | Primary end point(s) |
Pathologic coplete responseafter neoadjuvant treatment |
Risposta patologica copleta dopo terapia neoadiuvante |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of neoadjuvant treatment |
Alla fine della terapia adiuvante |
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E.5.2 | Secondary end point(s) |
ORR before surgery; ; Tumor regression rate; Rate of radical resection; Median relapse free survival; Evaluation of quality of life; Safety and tolerability of chemotherapy regimen (Neoadjuvant and adjuvant) |
Risposta globale prima della chirurgia; Grado di regressione tumorale; Rate di resezioni radicali; Mediana della sopravvivenza libera da recidiva; Valutazione della qualit¿ della vita; Sicurezza e tollerabilit¿ del regime chemioterapico (neoadiuvante e adiuvante) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After cycle 4 of neoadjuvant treatment; At the end of neoadjuvant treatment; At surgery; One year from surgery; At enrolment, at the end of neoadjuvant regiment, before surgery and at the end of treatment visit; From Informed consent signature to the end of treatment visit |
Dopo il ciclo 4 del trattamento neoadiuvante; Alla fine del trattamento neoadiuvante; Al momento della chirurgia; A un anno dalla chirurgia; All'arruolamento, alla fine della terapia neoadiuvante, prima della chirurgia e alla visita di fine trattamento; Dalla firma del consenso informato alla visita di fine trattamento |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers analysis |
Analisi di biomarcatori |
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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) | 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 | No |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |