| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| pazienti affetti da metastasi epatiche di carcionoma colorettale, operabili ad alto rischio o operabili "borderline" |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients affected by colorectal metastases to the liver only |
| Pazienti affetti da metastasi epatiche di carcionoma colorettale, operabili ad alto rischio o operabili "borderline" |
|
| 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 | 10061451 |
| E.1.2 | Term | Colorectal 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 |
| major pathologic response |
| risposta patologica maggiore |
|
| E.2.2 | Secondary objectives of the trial |
| radiologic response, pfs, safety, overall survival |
| risposta radiologica, sopravvivenza libera da progressione, sopravvivenza globale, sicurezza |
|
| 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 |
| traslational research on tissue biomolecular factors |
| ricerca traslazionale sui fattori biomolecolari tissutali |
|
| E.3 | Principal inclusion criteria |
- Histological diagnosis of colorectal adenocarcinoma.
- Liver-limited metastases or metastases mainly (≥80% total disease burden) limited to the liver with extraepatic disease judged resectable concomitantly or sequentially. Primary tumor may be resected or not, but patient must not be symptomatic for T.
- Previous adjuvant therapy is allowed if it had been terminated for at least 6 months.
- Previous first line treatment (irinotecan or oxaliplatin containing regimen) with stable or partial response after no more than 3 months of treatment
- Age >= 18 years
- Performance Status (ECOG <2)
- Adequate organ function including the following:
- Adequate bone marrow reserve: WBC count >3.0x109/L, absolute neutrophyl count >1.5x109/L, platelet count >100x109/L, and hemoglobin >10 g/dL .
- Hepatic: bilirubin < 1.5 times the ULN, alkaline phosphatase, aspartate transaminase, and alanine transaminase < 2.5 xULN
- Renal : serum creatinin <2.0xULN
- Patients compliance and geografic proximity that allows for adequate follow-up
- Patients must sign an informed consent document (ICD)
- Male and female patients with reproductive potential must use an approved contraceptive method.
|
- Adenocarcinoma del colon o del retto, confermato istologicamente.
- Malattia metastatica limitata al fegato o prevalentemente limitata al fegato. Il tumore primario può essere stato o meno resecato, ma non deve dare sintomatologia al paziente. La malattia epatica deve essere considerata a resecabilità borderline o resecabile ad alto rischio secondo i criteri istituzionali.
- Precedente terapia adiuvante, a condizione che siano trascorsi 6 mesi tra la fine della terapia e l’arruolamento nello studio
- Meno di tre mesi trascorsi da una precedente terapia di prima linea (regime contenente oxaliplatino o irinotecan), che non abbia dato evidenza di progressione di malattia (risposta parziale o malattia stabile)
- Età > 18 anni
- Performance Status ECOG <2
- Adeguata funzionalità midollare, epatica e renale; nello specifico:
Midollo osseo: conta assoluta dei leucociti (WBC) >3.0x109/L, conta assoluta dei neutrofili (ANC) >1.5x109/L, conta piastrinica >100x109/L ed emoglobina >10 g/dL .
Fegato: bilirubina totale < 1.5 x ULN (limite superior di normalità); fosfatasi alcalina, aspartato transaminasi e alanina transaminasi < 2.5 x ULN
Rene : creatinina sierica <2.0 x ULN
- Capacità e volontà da parte del paziente di firmare il consenso informato e di aderire al protocollo dello studio: è necessaria quindi una prossimità geografica, per consentire un adeguato follow-up.
I pazienti di entrambi sessi in età fertile devono utilizzare un metodo di contraccezione approvato ed efficace durante il periodo di trattamento sperimentale.
|
|
| E.4 | Principal exclusion criteria |
- Tumor involvement of liver > 75%
- Chance of a liver remnant after surgery < 25%
- Eligibility for concurrent radiotherapic treatment
- Disease progression during first line chemotherapy with FOLFOX, XELOX, FOLFIRI or XELIRI plus bevacizumab
- Previous treatment with more than 3 months of FOLFOX or FOLFIRI
- Previous therapy with bevacizumab or cetuximab or panitumumab
- Administration of other experimental drugs during the study.
- Body Mass Index > 35
- Brain metastases.
- Pregnancy and breast-feeding.
- Serious or uncontrolled medical pathologies or active infections that would jeopardize the possibility of receiving the investigated treatment. Disorders that could influence the absorption of capecitabine (e.g. malabsorption), intestinal occlusion, Crohn's disease or ulcerative colitis.
- Psychiatric disorders, neurologic disease or other conditions that would make it impossible to comply with the protocol procedures. Peripheral neuropathy not related to oxaliplatin previous administration.
- Previous dangerous life threatening toxicities from fluoropirimidine.
- Positive anamnesis with regard to other neoplastic diseases except for the ones that have been cured for more than 5 years.
|
malattia metastatica extra-epatica > 20% oppure giudicata non resecabile con intento in concomitanza o in sequenza.
- Coinvolgimento epatico > 75%
- Volume epatico residuo dopo chirurgia previsto come < 25%
- Trattamento radioterapico concomitante
- Evidenza di progressione di malattia durante la chemioterapia di prima linea con FOLFOX, XELOX, FOLFIRI or XELIRI più bevacizumab
- Trattamento precedente con FOLFOX o FOLFIRI di una durata di più di tre mesi
- Precedente terapia con bevacizumab or cetuximab or panitumumab
- Somministrazione di altri farmaci sperimentali durante lo studio.
- Indice di Massa Corporea > 35
- Metastasi Cerebrali.
- Gravidanza e allattamento.
- Infezioni attive o condizioni mediche serie pre-esistenti che potrebbero compromettere la possibilità del paziente di essere sottoposto al trattamento del protocollo; altre condizioni mediche che potrebbero influenzare l’assorbimento della capecitabina (per esempio malassorbimento, occlusione intestinale, malattia di Crohn o colite ulcerosa).
- Disordini psichiatrici, malattie neurologiche e alter condizioni mediche che non permetta l'aderenza alle procedure dello studio - Neuropatie periferiche non correlate alle precedenti somministrazioni di oxaliplatino.
- Grave tossicità indotta dalla terapia con fluoropirimidine.
Anamnesi di neoplasie maligne in alter sedi; sono invece eleggibili pazienti con neoplasie maligne e intervallo libero da malattia superiore a 5 anni.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| major pathologic response |
| remissione patologica maggiore |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| radiologic response, pfs, safety, overall survival |
| risposta radiologica, sopravvivenza libera da progressione, sopravvivenza globale, sicurezza |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 |
| prognostic biomarkers |
| biomarkers prognostici |
|
| 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
| 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
|
|
| 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 | |
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