E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Peritoneal carcinomatosis |
Carcinosi peritoneale |
|
E.1.1.1 | Medical condition in easily understood language |
Metastases to the peritoneum |
Metastasi al peritoneo |
|
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 | LLT |
E.1.2 | Classification code | 10068069 |
E.1.2 | Term | Peritoneal carcinomatosis |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The main objective of the study is to determine the effectiveness of PIPAC technique in patients with peritoneal metastases, who are not eligible for curative surgical resection. |
Verificare l'attività della tecnica PIPAC in pazienti con metastasi peritoneali che non sono candidabili alla resezione chirurgica con intento curativo |
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E.2.2 | Secondary objectives of the trial |
Secondary aims are to determine - the feasibility of the study treatment - the safety of the PIPAC technique - the antineoplastic activity - preliminary data on progression free survival (PFS) and overall survival (OS) - the quality of life (HRQoL) |
Obbiettivi secondari sono determinare: - la fattibilità del trattamento - la sicurezza della tecnica PIPAC - l'attività antineoplastica - dati preliminari sulla progressione libera da malattia e sulla sopravvivenza complessiva - l'andamento della qualità della vita correlata alla salute |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female = 18 years of age - ECOG performance status 0–2. - Histologically or cytologically documented gastrointestinal or ovarian cancer (based on tissue from the primary tumor and/or its metastases); other cancer can be included based on a careful multidisciplinary assessment of the risk benefit of the procedure in the specific patient - Radiological, histological or cytological evidence of peritoneal metastases - Not eligible for curative surgery and/or HIPEC according to National Guidelines - ife expectancy of at least 24 weeks; - Laboratory Requirements: - Neutrophils = 1.5 x 109/L; - Platelets = 100 x 109/L; - Hemoglobin = 9 g/dL; - Total bilirubin = 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) = 2.5 x UNL; - Alkaline phosphatase = 2.5 x UNL; - Creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula or serum creatinine =1.5 x UNL; - Negative serum or urine pregnancy test at screening for women of childbearing potential. Female subjects, or male subjects with female partners of child-bearing potential must be willing to use highly effective contraception as approved by the investigator (i.e. barrier contraceptive measure or oral contraception, total abstinence) during the study and until 30 days after last study treatment; - Written informed consent to the study participation according to the Local Ethic Committee requirements before any study procedure; - Will and ability to comply with the protocol. |
- soggetti adulti (età maggiore di 18 anni) di sesso maschile o femminile; - buon performance status (ECOG 0-2) - diagnosi confermata di neoplasia di origine colorettale, gastrica, o ginecologica (ovaio). Altre diagnosi istologiche tra cui pancreato-biliare, uro-genitale, tessuti molli o di altre rare origini potranno essere incluse previa attenta valutazione multidisciplinare del rischio beneficio atteso del trattamento nel singolo caso; - evidenza radiologica, istologica o citologica di metastasi peritoneale - paziente non candidabile ad intervento di chirurgia citoriduttiva con intento radicale; - funzione renale, epatica e midollare compatibile con la procedura PIPAC; - donne in età fertile e uomini sessualmente attivi dovranno utilizzare metodi contraccettivi efficaci durante tutto lo studio - in grado di comprendere le finalità dello studio e di fornire un valido consenso scritto alla partecipazione dello studio. |
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E.4 | Principal exclusion criteria |
- Any surgery apart from staging laparoscopy less than 4 weeks before inclusion; - Extra peritoneal metastasis; patients with limited extra peritoneal metastatic disease can be enrolled based on mdt discussion; - Bowel obstruction or parenteral nutrition or gastric tube; - A history of allergic reaction or contraindication to platinum containing compounds or doxorubicin; - Any significant disease which, in the investigator’s opinion, excludes the patient from the study; - Myocardial insufficiency, defined as NYHA class >3 - Renal impairment, defined as glomerular filtration rate (GFR) < 30 ml/min - Impaired liver function defined as bilirubin > 1.5 UNL (except in presence of Gilbert disease) - Pregnancy or breastfeeding; - Untreated central nervous system disease, history or evidence of thrombotic or hemorrhagic disorders not considered currently in complete remission; - Active infection requiring antibiotics; - Medical, geographical, sociological, psychological, or legal conditions that would prevent the patient from completing the study or signing the informed consent; |
- paziente sottoposto a chirurgia nelle 4 settimane precedenti all’inclusione nello studio; - occlusione intestinale, nutrizione parenterale o sondino nasogastrico; - presenza di metastasi extraperitoneali; pazienti con malattia minima extraperitoneale trattabile con intento curativo possono essere inclusi in seguito a valutazione multidisciplinare - anamnesi positiva per reazione allergica ai composti del platino o alla doxorubicina - trattamenti precedenti con massima dose cumulativa per i chemioterapici in studio - insufficienza cardiaca, renale od epatica non controllata dalle terapie farmacologiche in atto; - gravidanza; - incapacità o mancanza di volontà a dare consenso informato scritto. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the histological response to treatment, assessed using the peritoneal regression grading system (PRGS) score. Response to treatment will be assessed comparing the PRGS score at each PIPAC procedure respect to the PRGS score at the first PIPAC procedure (baseline). Patients, who did not receive at least three procedures, will be considered non responders. The PRGS score distinguishes between four grades of tumor regression, PRGS 1–4. PRGS 1 (complete response) is defined as no tumor cells present; PRGS 2 (major response) is regressive changes predominant over tumor cells; PRGS 3 (minor response) is predominance of tumor cells but regressive changes present, and PRGS 4 (no response) is no regressive changes present. At least four peritoneal punch biopsies of 3 to 5mm in diameter should be taken in all four abdominal quadrants, plus a centimetric peritonectomy of not-affected peritoneum (to be used as reference). The PRGS score will be reported as the mean and the worst value of the regression grades obtained. When complete tumor response is suspected intraoperatively, a peritoneal cytology should be sampled. A histological tumor response is defined as a decrease of 0.5 in the mean PRGS score. Tumor response rate is defined as the portion of participants with a histological tumor response. |
Risposta patologica valutata mediante Peritoneal Regression Grading System |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At second and third PIPAC procedure after 6 or 8 weeks and 12 or 16 weeks after first PIPAC procedure. |
Alla seconda e terza PIPAC dopo rispettivamente 6-8 e 12-16 settimane dopo l'esecuzione della prima PIPAC |
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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 | 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
|
Last safety visit after the third PIPAC procedure in the last enrolled patient |
Ultima visita di sicurezza dopo terza procedura PIPAC nell'ultimo paziente arruolato. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |