E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient with potentially resectable adenocarcinoma of the stomach |
Pazienti con carcinoma dello stomaco potenzialmente resecabile |
|
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 | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
The percentage of patients receiving all the planned chemotherapeutic cycles. |
La percentuale dei pazienti che hanno ricevuto tutti i cicli di chemioterapia programmati. |
|
E.2.2 | Secondary objectives of the trial |
• Downstaging according to Recist criteria • pT1-3 vs pT0. • Safety: number of patients with grade 3-4 toxicity • The role of PET Scan as predictor of response • Curative vs palliative surgery • TTP • OS • Diagnostic correlation between the various staging methods • Possible correlations between CT scan, CT/PET, laparoscopy; • Molecualr marker related to toxicity: DPYD, MTHFR, TS, XPD, ERCC1, XRCC1; • Molecular marker related to prognosis: TYMS, GSTP1, COX-2, RUNX3, methylation profile (Cox2, hMLH1, MGMT); • Molecular marker related to therapy response: TYMS, DPYD, MTHFR, OPRT, ERCC1, XRCC1/2/3, GSTP1, GSTM1, GSTT1, ABCB1, methylation profile (Cox2, hMLH1, MGMT), whole genome arrayCGH |
• Downstaging secondo i criteri RECIST • pT1-3 vs pT0. • Sicurezza: numero di pazienti con grado 3-4 di tossicita' • Ruolo della PET come predittore di risposta • Chirurgia curativa vs chirurgia palliativa • TTP • OS • Correlazione diagnostica fra i vari metodi di staging • Possibile correlazione fra TAC, TAC/PET, laparoscopia; • Markers molecolari relativi alla tossicita': DPYD, MTHFR, TS, XPD, ERCC1, XRCC1; • Markers molecolari relativi alla prognosi: TYMS, GSTP1, COX-2, RUNX3, profilo di metilazione (Cox2, hMLH1, MGMT); • Markers molecolari relativi alla risposta alla terapia: TYMS, DPYD, MTHFR, OPRT, ERCC1, XRCC1/2/3, GSTP1, GSTM1, GSTT1, ABCB1, profilo di metilazione (Cox2, hMLH1, MGMT), whole genome arrayCGH. |
|
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:1.0
Date:2010/06/01
Title:
Objectives:
|
FARMACOGENETICA:
Vers:1.0
Data:2010/06/01
Titolo:STUDIO DI FASE II RANDOMIZZATO CON DOCETAXEL, OXALIPLATINO, CAPECITABINA (DOX) COME TRATTAMENTO PREOPERATORIO O PERIOPERATORIO (PRIMA E DOPO LA
GASTRECTOMIA) IN PAZIENTI CON CARCINOMA GASTRICO LOCALMENTE AVANZATO RESECABILE.
Gastric neoadjuvant, biological study
Obiettivi:• Markers molecolari relativi alla tossicita': DPYD, MTHFR, TS, XPD, ERCC1, XRCC1;
• Markers molecolari relativi alla prognosi: TYMS, GSTP1, COX-2, RUNX3, profilo di metilazione (Cox2, hMLH1, MGMT);
• Markers molecolari relativi alla risposta alla terapia: TYMS, DPYD, MTHFR, OPRT, ERCC1, XRCC1/2/3, GSTP1, GSTM1, GSTT1, ABCB1, profilo di metilazione (Cox2, hMLH1, MGMT), whole genome arrayCGH.
|
|
E.3 | Principal inclusion criteria |
• Male or female 18-75 years of age
• Diagnosis of histologically confirmed, potentially resectable adenocarcinoma of the stomach
• cT3 subserosal - cT4a – cT4b (7th edition UICC TNM) or bulky lymph node metastases independently of T
• ECOG performance status 0-1 at study entry
• Laboratory requirements (up to 8 days prior to randomization):
a) Haematology:
I) Neutrophils > 1.5 x 109 /L
II) Platelets > 100 x 109 /L
III) Hemoglobin > 10g/dL
b) Hepatic function
I) Total bilirubin < 1.25 UNL
II) AST (SGOT) and ALT (SGPT)<2.5xUNL
II) Alkaline phosphatase < 2.5xUNL c) Renal function
I) Creatinine <1.5 UNL
In the presence of border-line values, the calculated creatinine clearance should be >= 60 mL/min;
• Written informed consent signed and dated before randomization procedures, must be obtained and documented according to the local regulatory requirement.
• Effective contraception for both male and female patients if the risk of conception exists. |
. Maschi o femmine 18-75 anni di eta'
. Diagnosi istologicamente confermata di adenocarcinoma dello stomaco
potenzialmente resecabile
. cT3 sottosierosa - cT4a – cT4b (7th edizione UICC TNM) o metastasi
linfonodali indipendentemente da T
. ECOG performance status 0-1 all’ingresso in studio
. Requisiti di laboratorio (fino a 8 giorni prima della randomizzazione):
a) Ematologia:
I) Neutrofili > 1.5 x 109 /L
II) Piastrine > 100 x 109 /L
III) Emoglobina > 10g/dL
b) Funzionalita' epatica
I) Bilirubina totale < 1.25 UNL
II) AST (SGOT) e ALT (SGPT) < 2.5xUNL
III) Fosfatasi alcalina < 2.5xUNL
c) Funzionalita' renale
I) Creatinina <1.5 UNL
In presenza di valori border-line, la clearance della creatinina
calcolata dovrebbe essere >= 60 mL/min;
· Un consenso informato scritto firmato e datato deve essere ottenuto e
documentato secondo le esigenze locali di regolamentazione, prima delle
procedure di randomizzazione.
· Se esiste il rischio di concepimento, deve essere utilizzato un
contraccettivo efficace sia per i pazienti maschi e che per le pazienti
femmine. |
|
E.4 | Principal exclusion criteria |
• Early gastric cancer (if N0)
• T2 (according to 7th edition of UICC TNM) if N0
• Linitis plastica
• Positive peritoneal cytology
• Distant metastases
• Tumor involving the gastro-esophageal junction
• Peritoneal involvement
• Concurrent chronic systemic immune therapy
• Any investigational agent(s) 4 weeks prior to study entry
• Clinically relevant coronary artery disease, a history of myocardial infarction or a history of hypertension not controlled by therapy within the last 12 months
• Known grade 3 or 4 allergic reaction to any of the components of the treatment
• Known drug abuse/alcohol abuse
• Legal incapacity or limited legal capacity
• Medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent
• Women who are pregnant or breastfeeding
• Acute or subacute intestinal occlusion
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial) |
. Early gastric cancer (se N0)
. T2 (secondo la 7th edizione della UICC TNM) se N0
. Linite plastica
. Citologia peritoneale positiva
. Metastasi a distanza
. Tumori che coinvolgono la giunzione gastro-esofagea
. Coinvolgimento peritoneale
. Concomitante terapia sistemica immunitaria
. Utilizzo di qualsiasi agente sperimentale nelle 4 settimane precedenti lo studio
. Malattia coronaria clinicamente significativa, storia di infarto al
miocardio o storia di ipertensione non controllata entro gli ultimi 12 mesi
. Reazione allergica nota di Grado 3 o 4 ad uno qualsiasi dei componenti
del trattamento
. Abuso noto di farmaci e alcol
. Incapacita' legale o limitata capacita' legale
. Condizione medica o psicologica che, ad opinione del medico, non
potrebbe consentire al paziente di completare lo studio o firmare il
consenso informato
. Donne che sono incinte o che allattano
. Occlusione intestinale acuta o subacuta
. Qualsiasi altra neoplasia diversa dal tumore cutaneo non melanoma o
carcinoma in situ della cervice. (Pazienti con precedente neoplasia ma
senza evidenza di malattia per un periodo ≥ 5 anni potranno entrare in
studio) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients receiving all the planned chemotherapeutic cycles. |
La percentuale dei pazienti che hanno ricevuto tutti i cicli di chemioterapia programmati |
|
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 | 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 | 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 |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 80 |
E.8.9.1 | In the Member State concerned days | 0 |