E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer |
Pacientes que tendrán una cirugía de citoreducción máxima por una carcinomatosis peritoneal de origen colorrectal |
|
E.1.1.1 | Medical condition in easily understood language |
Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer |
Pacientes que tendrán una cirugía de citoreducción máxima por una carcinomatosis peritoneal de origen colorrectal |
|
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 | LLT |
E.1.2 | Classification code | 10052171 |
E.1.2 | Term | Peritoneal carcinoma |
E.1.2 | System Organ Class | 100000004864 |
|
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 compare the overall survival in patients affected with peritoneal carcinosis of colorectal origin and having undergone a macroscopically complete or suboptimal (with unresected residual tumor tissues ? 1mm) surgical resection and benefiting from a maximized treatment with chemotherapy (i.e.: maximal surgery + chemohyperthermia + pre- or post-operatory systemic chemotherapy) or a maximized treatment without chemohyperthermia (i.e.: maximal surgery + pre-or post-operatory systemic chemotherapy). |
Comparar la supervivencia global en pacientes con carcinomatosis peritoneal de origen colorrectal que hayan sido sometidos a una cirugía citoreductora completa macroscópicamente o subóptima (residuo tumoral menor de 1 mm) , complementándola con quimiohipertermia y quimioterapia sistémica o bien , sólo con quimioterapia sistémica. |
|
E.2.2 | Secondary objectives of the trial |
?Evaluate recurrence-free survival of these patients. ?Evaluate treatment toxicities. ?Determine morbidity from surgical complications. ?Determine prognostic factors of survival. |
- Evaluar la supervivencia sin recidiva -Evaluar la toxicidad del tratamiento (CTC-AE v3.0) -Evaluar la tasa de morbilidad -Evaluar los factores pronósticos de supervivencia |
|
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 |
nutrition and digestive surgery study: aim: patient nutrition evaluation treated for a peritoneal carcinomatosis before and 3 months after the surgery. Correlation between nutritional status and complications to mesure specific morbidity To study patient evolution |
-Estudio sobre nutrición y cirugía digestiva: objetivos: -evaluación nutricional de los pacientes en tratatmiento por una carcinomatosis peritoneal antes y 3 meses después de la cirugía -Correlación entre estado nutricional y complicaciones -Medir la morbilidad más específicamente -Estudiar la evolución de los pacientes |
|
E.3 | Principal inclusion criteria |
1) Histologically confirmed colorectal cancer, 2) Minimal or moderate peritoneal carcinosis with a Sugarbaker peritoneal score ? à 25 (see annex 9), (peroperatory assessment), 3) A surgically obtained tumor reduction, macroscopically complete R1 or with a residual thickness not exceeding 1 mm (R2), (peroperatory assessment) 4) Absence of extra peritoneal metastases including hepatic and pulmonary metastases ( confirmed by a PET scan, if possible), 5) Patient to be treated by systemic chemotherapy for its carcinosis, 6) 18 ? age ? 70 yo, 7) WHO performance status ? 1, 8) Life expectancy > 12 weeks, 9) Adequate hematological function: polynuclear neutrophiles ? 1,5x10 9 /L, platelets ? 100x10 9 /L, 10) Adequate hepatic function : total bilirubin ? 1,5 x ULN, ASAT (SGOT) and ALAT (SGPT) ? 3 x ULN, alkaline phosphatases ? 3 x ULN, 11) Seric creatinine ? 1,25 x ULN, 12) Operable patient, 13) Peripheral neuropathy with grade ? 3 (CTC AE v3.0 annex 7) 14) Patient information and written informed consent form signed before any protocol specific procedure is started. 15) Patient is affiliated with a proper/French national health insurance fund |
1) Cáncer colorrectal histológicamente demostrado 2) Carcinomatosis peritoneal de extensión leve o moderada , con un Score de extensión peritoneal de Sugarbaker menor a 25( Anexo 9) ( Evaluación intraoperatoria) 3) La obtención de una citorreducción quirúrgica macroscópicamente completa ( R1 ) o residuo tumoral no superior a 1 mm (R2), (evaluación intraoperatoria) 4) Ausencia de metástasis extraperitoneales, incluyendo metástasis hepáticas y pulmonares(si es posible confirmadas por la práctica de un PET) 5) Haber recibido tratamiento con quimioterapia sistémica. 6) Edad comprendida entre 18 y 70 años 7) Performance status OMS ≤ 1 8) Esperanza de vida> 12 semanas 9) Función hematológica: PNN ≥1,5 x 109/L, plaquetas 100x109/L, 10) Función hepática: bilirrubina total sin sobrepasar 1.5 veces los valores normales, AST (SGOT) y ALT (SGPT) sin sobrepasar 3 veces los valores normales. 11) creatinina plasmática sin sobrepasar 1.25 veces los valores normales. 12) Pacientes operables 13) Neuropatía periférica de grado 3 (CTC AE v 3.0, Anexo 7) 14) Información al paciente y firma de un consentimiento informado antes de cualquier procedimiento especifico del estudio 15) Afiliación a un régimen de seguridad social. |
|
E.4 | Principal exclusion criteria |
1) Carcinosis of other-than-colorectal origin, specifically appendiculary carcinomas, 2) Large volume carcinosis with Sugarbaker peritoneal-extent score >25 (annex 9), (peroperatory assessment) 3) Patient has already been treated by chemohyperthermia 4) History of previous cancer (except cutaneous basocellular carcinoma or in situ carcinoma of the uterine cervix) with a relapse occurred within the 5-year period prior to inclusion, 5) Patient already included in another first-line therapeutic trial aimed at the same disease study, 6) Pregnant women, women who are likely to become pregnant or are breast-feeding, 7) Individual deprived of liberty or placed under the authority of a tutor, 8) Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. |
1) Carcinomatosis de cualquier otro origen, en particular el carcinoma apendicular. 2) Carcinomatosis peritoneal de extensión grave, con un Score de extensión peritoneal de Sugarbaker > 25 ( Anexo 9) (evaluación intraoperatoria) 3) Pacientes tratados previamente con quimiohipertermia 4) Antecedentes de cáncer (excepto el carcinoma de basocelular cutáneo o carcinoma in situ de cuello uterino) con recaída en los 5 años previos a la entrada en el estudio. 5) Paciente incluido en otro ensayo clínico de primera línea para la enfermedad estudiada 6) Embarazo (o sospecha del mismo), periodo de lactancia. 7) Las personas privadas de libertad o bajo tutela, 8) Incapacidad para someterse a examen médico por razones geográficas, sociales o psicológicas. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival will be taken into account. Estimate of the median survival is 30 months in the control group. The trial objective is to increase the median survival time to 48 months using the experimental treatment PICH (hazard ratio = 0.625). |
Se evaluará principalmente la supervivencia global. La media de supervivencia está estimada en 30 meses en el grupo control. El objetivo es aumentar la media de supervivencia hasta alcanzar los 48 meses en el tratamiento experimental CHIP (hasard ratio= 0,625) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Survival without relapse : the following cases will be considered as relapse : - Histologically confirmed relapse or a suggestive context (palpable nodules, visible on imaging, with concomitant elevation of significant markers) - Distant relapse (evident on imaging or Histologically confirmed), - Any patient's death.
Treatment toxicity : according to the CTC AE v3.0 scale (annex 7) Surgical complications : - Abdominal complications : (digestive fistula, urinary fistula, deep abscess without fistula, hemoperitoneum, number of percutaneous drainages) - Extra-abdominal complications: (pulmonary, infectious urinary, central catheter infection, venous (thrombo-embolic), parietal, renal insufficiency, cardiac disorders) - Aplasia: postoperatory, febrile aplasia or other non-febrile complications.
Morbidity : - Patients' deaths occurring within 60 days following surgery, - Serious hemorrhages (> 30 % of blood volume), - Serious hemodynamic impairments, - Any visceral impairments, notably : o Renal insufficiency or rhabdomyolysis requiring dialysis. o Respiratory impairment requiring assisted ventilation = 2 days. o Hepatic impairment: bilirubine > 10 N. o Serious neurophysiological and motricity disorders. - Parenteral feeding at home > 1 month, - Any infectious complication (locoregional infection, abscess drainage?.) - Grade 4 thrombopenia (< 25 000), Neutropenia < 500 PN, blood transfusion > 4 CG, Diarrheas > 15 times/day and beyond D21, serious decrease of auditive capacity, - Any SAE putting the vital prognosis at stake or causing permanent invalidity or serious temporary incapacity. -Survival prognostic factors |
1- Supervivencia sin recidiva, siendo consideradas recidivas: - Recidiva peritoneal demostrada histológicamente o contexto clínico muy sugestivo (Nódulos palpables o hallados en prueba de imagen con elevación concomitante de marcadores tumorales). - Recidiva a distancia (evidente en la iconografía o comprobada histológicamente) - Las muertes por todas las causas. 2- La toxicidad del tratamiento: de acuerdo con CTC AE v3.0 (Anexo 7) 3- Complicaciones quirúrgicas: - Complicaciones abdominales (Fístula digestiva, fístula urinaria, absceso profundo sin fístula, hemoperitoneo, número de drenajes percutáneos) - Complicaciones extra-abdominales: (pulmonares, infección urinaria, infección del catéter central, venosas (tromboembolismo), parietal, insuficiencia renal, cardiacas) - Aplasia postoperatoria, aplasia febril o complicaciones no febriles. 3- Morbilidad: - Mortalidad en los 60 días después de la cirugía, - Sangrado severo (> 30% del volumen sanguíneo) - Inestabilidad hemodinámica severa, - Toda insuficiencia orgánica, en especial, Insuficiencia renal o rabdomiolisis que requiera diálisis Fracaso respiratorio que requiera ventilación asistida = 2 días Insuficiencia hepática : bilirrubina> 10 N. Alteraciones cerebro-motoras graves - Nutrición parenteral > 1 mes a domicilio - Cualquier complicación infecciosa (infección locorregional, drenaje de abscesos ....) - Trombocitopenia grado 4 (<25 000), neutropenia <500 PN, transfusión> 4 concentrados de hematíes, diarrea > 15 deposiciones / día más allá del día 21 hipoacusia severa -Todos los efectos adversos graves que comprometan la vida o provoquen una invalidez permanente o una incapacidad temporal grave. 4- Factores pronósticos de supervivencia |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
maximal surgery without chemohyperthermia |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Yes |
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 | 7 |
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 | 7 |
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 |