| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with colon adenocarcinoma (proximal to peritoneal reflection) in stage pT4a / b, N0-2, M0, or with primitive perforated tumor undergoing curative surgery. |
| Pazienti con adenocarcinoma del colon (prossimale alla riflessione peritoneale) in stadio pT4a/b, N0-2, M0, o con tumore primitivo perforato sottoposti a chirurgia curativa. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with colon adenocarcinoma (proximal to peritoneal reflection) in stage pT4a / b, N0-2, M0, or with primitive perforated tumor undergoing curative surgery. |
| Pazienti con adenocarcinoma del colon (prossimale alla riflessione peritoneale) in stadio pT4a/b, N0-2, M0, o con tumore primitivo perforato sottoposti a chirurgia curativa. |
|
| E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10055114 |
| E.1.2 | Term | Colon cancer metastatic |
| 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 |
| Primary Objective: of this study is to demonstrate the effectiveness of adjuvant PIPAC performed within 4-8 weeks after curative-intent surgery, and followed by adjuvant s-CT, in preventing the onset of PM in high risk colon cancer. |
| L’obiettivo primario i questo studio è dimostrare l’efficacia nel prevenire l’insorgenza di metastasi peritoneali della PIPAC adiuvante, eseguita entro 4-8 settimane dopo intervento resettivo, con intento curativo per cancro del colon, e seguita da s-CT adiuvante, in pazienti ad alto rischio. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary Objectives: are to assess feasibility, toxicity and impact on the quality of life (QoV) of the adjuvant PIPAC, performed in an early setting (within 4-8 weeks of primitive surgery), overall survival, disease-free survival (peritoneal and distant), and pattern of disease progression after the procedure |
| Gli obiettivi secondari sono la fattibilità, la tossicità e l’impatto sulla qualità di vita (QdV) della PIPAC adiuvante, eseguita in un setting precoce (entro 4-8 settimane dalla chirurgia del primitivo), la sopravvivenza globale, la sopravvivenza libera da malattia (peritoneale e a distanza), e il pattern di progressione di malattia dopo la procedura. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) histopathologically confirmed intestinal-type, mucinous or signet ring cell adenocarcinoma of the colon (with upper limit of the tumor above the peritoneal reflection);
2) curative (microscopically complete) surgery performed by laparotomy or laparoscopy;
3) presence of at least one of the following risk factors for the development of metachronous PM:
- primary tumor infiltrating the visceral peritoneum (pT4a, N0-2b, M0);
- primary tumor directly invading adjacent organs (pT4b, N0-2b, M0);
- perforated primary tumor (any T, N0-2b, M0);
4) age >18;
5) performance status =2 according to the WHO score
6) willingness to start adjuvant systemic therapy and post-operative follow-up;
7) signature of informed consent. |
1. adenocarcinoma del colon di tipo intetstinale, mucinoso o a cellule ad anello con castone isto-patologicamente confermato (con limite superiore del tumore a monte della riflessione peritoneale);
2. chirurgia curativa (macroscopicamente completa) eseguita per via laparotomica o laparoscopica;
3. presenza di almeno uno dei seguenti fattori di rischio per lo sviluppo di MP metacrone:
• tumore primitivo infiltrante il peritoneo viscerale (pT4a, N0-2b, M0),
• tumore primitivo che invade direttamente altri organi adiacenti (pT4b, N0-2b, M0);
• tumore primitivo perforato (ogni T, N0-2b, M0)
4. età> 18;
5. performance status =2 secondo lo score WHO;
6. disponibilità a iniziare terapia sistemica adiuvante e follow-up postoperatorio;
7. firma del consenso informato |
|
| E.4 | Principal exclusion criteria |
1) active sepsis;
2) impaired cardiac function (history of previous heart failure or 40% FE);
3) impaired renal function (serum creatinine >1.5 normal value or creatinine clearance < 60 ml/min);
4) impaired liver function (AST, ALT, bilirubin > 1.5 normal value);
5) impaired bone marrow function (leukocytes <4000/mm3, neutrophils <1500/mm3, platelets <80000/mm3);
6) impaired lung function (diagnosis of severe COPD or 50% FEV1 or 40% DLCO adjusted for age);
7) presence of extra-abdominal and/or hepatic metastases at CT scan of the chest, abdomen and pelvis with an intravenous contrast medium;
8) severe complications (grade 3-4) after primary cancer surgery;
9) haemorrhagic diathesis or coagulopathy;
10) pregnancy or lactation in progress;
11) psychiatric or neurological conditions that preclude the procedures of the protocol;
12) contraindications to laparoscopy;
13) known hypersensitivity to oxaliplatin or other platinum containing compounds and/or to any of their excipients;
14) history of previous malignancies treated in the last three years, excluding cutaneous spinocellular carcinoma and/or basocellular carcinoma;
15) prior pre-operative radio-chemotherapy. |
1. sepsi attiva;
2. alterata funzionalità cardiaca (anamnesi di precedente insufficienza cardiaca o FE <40%);
3. alterata funzionalità renale (creatinina sierica >1,5 valore normale o clearance della creatinina <60 ml/min);
4. alterata funzionalità epatica (AST, ALT, bilirubina > 1.5 valore normale);
5. alterata funzionalità midollare ossea (leucociti <4000 / mm3, neutrofili <1500 /mm3, piastrine <80000/mm3);
6. alterata funzionalità polmonare (diagnosi di BPCO grave o FEV1 <50% o DLCO <40% aggiustato per età);
7. presenza di metastasi extra-addominali e/o epatiche alla TAC di torace, addome e pelvi con mezzo di contrasto endovenoso;
8. complicanze severe (grado 3-4) dopo la chirurgia del tumore primitivo;
9. diatesi emorragica o coagulopatia;
10. gravidanza o allattamento in atto;
11. patologie psichiatriche o neurologiche tali da precludere le procedure previste dal protocollo;
12. Controindicazioni alla laparoscopia
13. ipersensibilità nota all'oxaliplatino o ad altri composti contenenti platino e / o ad uno qualsiasi dei loro eccipienti;
14. anamnesi positiva per pregresse neoplasie trattate negli ultimi tre anni, escluso il carcinoma spinocellulare e/o basocellulare cutaneo;
15. pregressa radio-chemioterapia preoperatoria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The efficacy of adjuvant PIPAC will be assessed by measuring peritoneal metastasis-free survival from the date of primary surgery to the date of MP diagnosis. |
| L’efficacia della PIPAC adiuvante sarà valutata misurando la sopravvivenza libera da metastasi peritoneali dalla data della chirurgia del tumore primitivo alla data della diagnosi di MP. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The adjuvant PIPAC performed in an early setting after primary surgery will be considered feasible if:
•the laparoscopic procedure can be completed in 9 patients;
•the postoperative stay will be three days or shorter in =6 patients;
•the post-operative adjuvant s-CT will begin within 12 weeks of primary surgery in = 9 patients.
The adjuvant PIPAC will be considered a well tolerated procedure if:
•a maximum of one serious treatment-related complication will occur;
•a maximum of one laparotomy conversion will occur;
•a maximum of one hospital readmission will occur within 30 days.
Overall survival will be measured from the date of primary cancer surgery to the date of death for any cause or, for patients still alive at the date of the last available follow-up (Kaplan-Meier).
Disease-free survival will be measured from the date of primary cancer surgery to the date of MP diagnosis, systemic metastases or patient death.
The pattern of disease recurrence after adjuvant PIPAC will be determined by recording the anatomical site and date of onset of both metacrone MP, as well as metacrone systemic metastasis (extraperitoneal), and deaths.
QoV will be evaluated with EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires |
La PIPAC adiuvante eseguita in un setting precoce dopo la chirurgia del primitivo sarà considerata fattibile se:
• sarà possibile portare a termine l’accesso laparoscopico in =9 pazienti;
• la degenza postoperatoria sarà di tre giorni o più breve in =6 pazienti;
• la s-CT adiuvante post-operatoria inizierà entro 12 settimane dall'intervento chirurgico sul primitivo in = 9 pazienti.
La PIPAC adiuvante sarà considerata una procedura ben tollerata dal paziente se:
• si verificherà un massimo di una complicanza grave correlata al trattamento;
• si verificherà un massimo di una conversione laparotomica;
• si verificherà un massimo di un rientro in ospedale entro 30 giorni dalla PIPAC.
La sopravvivenza complessiva sarà misurata dalla data della chirurgia del tumore primitivo alla data del decesso per qualsiasi causa o, per i pazienti ancora in vita alla data dell’ultimo follow-up disponibile (Kaplan-Meier).
La sopravvivenza libera da malattia sarà misurata dalla data della chirurgia del tumore primitivo alla data della diagnosi di MP, di metastasi sistemiche o di decesso del paziente.
Il pattern di recidiva di malattia dopo PIPAC adiuvante sarà determinato registrando la sede anatomica e la data di insorgenza sia delle MP metacrone, che delle metastasi sistemiche (extraperitoneali) metacrone, e i decessi.
La QdV sarà valutata con i questionari EORTC QLQ-C30, EORTC QLQ-CR29. |
|
| 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 | 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 | 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| 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
|
|
| 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 | 30 |
| 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 | 30 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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