| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Cancer colorectal stage IV with synchronous non-resectable metastasis. |
| Pacientes con cáncer colo-rectal con metástasis sincrónicas irresecables. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer colorectal stage IV with synchronous non-resectable metastasis. |
| Pacientes con cáncer colo-rectal con metástasis sincrónicas irresecables. |
|
| 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 | 16.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10010035 |
| E.1.2 | Term | Colorectal cancer stage IV |
| 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 |
| In patients with colorectal cancer with unresectable synchronous metastases. To determine overall survival increases in resection of the primary tumor and subsequent treatment with palliative chemotherapy (experimental group) compared with treatment with palliative chemotherapy exclusive (control group). |
| Determinar si la resección del tumor primario y el tratamiento posterior con quimioterapia paliativa (grupo experimental) aumenta la supervivencia global, comparada con el tratamiento exclusivo con quimioterapia sistémica (grupo control) en pacientes con cáncer colo-rectal con metástasis sincrónicas irresecables. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the postoperative morbidity and mortality in patients treated with resection of the primary tumor.
- To evaluate the need for surgery and complications in patients treated with systemic chemotherapy exclusively during the course of the disease.
- To identify and describe the complications related to chemotherapy and toxicity in the short and medium term systemic treatment.
- To identify the prognostic factors for overall survival.
- To evaluate the costs associated with each treatment group.
- To compare the events between experimental and control groups. |
-Comparar la calidad de vida entre el grupo experimental y el grupo control (cuestionarios QLQ-C30 y QLQ-CR29).
-Evaluar la morbimortalidad postoperatoria en los pacientes tratados con resección del tumor primario.
-Evaluar las complicaciones y necesidad de cirugía en los pacientes tratados exclusivamente con quimioterapia sistémica durante el transcurso de la enfermedad.
-Determinar y describir las complicaciones relacionadas con la quimioterapia, así como la toxicidad a corto y medio plazo del tratamiento sistémico.
-Identificar los factores pronósticos de la supervivencia global.
-Evaluar los costes asociados a cada grupo de tratamiento.
-Comparar los acontecimientos entre el grupo experimental y el grupo control. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Primary adenocarcinoma of the colon or upper rectum. Only include rectal tumors located above 12 cm from the anal margin (the distance from the anal verge will be evaluated by rigid proctoscopy if in doubt).
- Radiologically resectable primary tumor (as CT or MRI).
or In the case of higher rectum tumor, no infiltration of vascular, nerve or bone.
or in cases of colorectal tumor invasion T4 with neighboring organs (abdominal wall, uterus, bladder, small intestine, liver segment, gall bladder, second or fourth portion of the duodenum, pancreas tail or greater curvature of the stomach) measured radical resection.
- No urgent or emergent surgery of the primary tumor by an event related to the same. In the case of occlusion and endoluminal stenting with clinical success, the patient may be included in the randomization.
- Radiological Confirmation unresectable synchronous metastases, both liver and in other locations. Unresectability criteria will be evaluated by a Committee of Experts on the Functional Unit of Colorectal Cancer of each center or by a multidisciplinary team.
- Absence of peritoneal carcinomatosis in the radiological study.
- Before completing any study-related procedures listed in Section 6.3, the patient must give informed consent to participate, in writing, signed and dated.
- Staging performed in less than 3 weeks prior to randomization.
- No contraindications for chemotherapy.
- ECOG performance status ? 2.
- Patient considered mentally and physically fit to receive chemotherapy and surgical treatment, judging by the multidisciplinary team.
- Age ? 18 years.
- Not pregnant or nursing.
- Negative pregnancy test in patients of childbearing age.
- Adequate monitoring potential. |
- Adenocarcinoma primario de colon o recto superior. Sólo se incluirán los tumores de recto localizados por encima de 12 cm del margen anal (la distancia al margen anal será evaluada por rectoscopia rígida en caso de duda).
- Tumor primario resecable radiológicamente (según TC o RNM).
o En el caso de tumor de recto superior, ausencia de infiltración de estructuras vasculares, nerviosas u óseas.
o En los casos de tumor colo-rectal T4 con invasión de órganos vecinos (pared abdominal, útero, vejiga urinaria, intestino delgado, segmento hepático, vesícula biliar, segunda o cuarta porción duodenal, cola de páncreas o curvatura mayor del estómago) se valorará su resección radical.
- No cirugía urgente o emergente del tumor primario por un evento relacionado con el mismo. En el caso de oclusión y colocación de un stent endoluminal con éxito clínico, el paciente podrá ser incluido en la aleatorización.
- Confirmación radiológica de metástasis sincrónicas irresecables, tanto hepáticas como en otras localizaciones. Los criterios de irresecabilidad serán evaluados por un Comité de Expertos en la Unidad Funcional de Cáncer Colo-rectal de cada centro o por un equipo multidisciplinar.
- Ausencia de carcinomatosis peritoneal en el estudio radiológico.
- Antes de completar cualquiera de los procedimientos relacionados con el estudio que se enumeran en la sección 6.3, el paciente deberá otorgar su consentimiento informado para participar, por escrito, firmado y fechado.
- Estadificación realizada en menos de 3 semanas antes de la aleatorización.
- No contraindicaciones para recibir quimioterapia.
- ECOG performance status ? 2.
- Paciente considerado mentalmente y físicamente apto para recibir quimioterapia y tratamiento quirúrgico, a juzgar por equipo multidisciplinar.
- Edad ?18 años.
- No embarazo o lactancia.
- Test de embarazo negativo en las pacientes en edad fértil.
- Adecuado potencial de seguimiento. |
|
| E.4 | Principal exclusion criteria |
- Infiltration of bone structures, vascular or nerve root infiltration of the superior mesenteric artery or the head of the pancreas.
- Presence of multiple bone metastatic disease or central nervous system.
- Concomitant neoplastic disease in the past 5 years except basal cell carcinoma or squamous skin or carcinoma "in situ" of the cervix.
- Medical or psychiatric condition that compromises the patient's informed consent authorization.
- Uncontrolled concomitant medical pathology or stable that could compromise the tolerance to chemotherapy.
- Patients with malabsorption syndromes or physical loss of the integrity of the upper digestive tract.
- Clinically significant cardiac pathology (congestive heart failure, symptomatic coronary artery disease) and myocardial infarction in the last 6 months.
- Patients with symptoms or symptoms of peripheral neuropathy.
- Refusal to participate in the study. |
- Infiltración de estructuras óseas, vasculares o nerviosas, infiltración de la raíz de la arteria mesentérica superior o de la cabeza de páncreas.
- Presencia de enfermedad metastásica ósea múltiple o del sistema nervioso central.
- Enfermedad neoplásica concomitante en los últimos 5 años a excepción de carcinoma escamoso o basocelular de piel o carcinoma ?in situ? de cérvix.
- Condición médica o psiquiátrica del paciente que comprometa la autorización del consentimiento informado.
- Patología médica concomitante no controlada o estable que pueda comprometer la tolerancia a la quimioterapia.
- Pacientes con síndromes de mala absorción o pérdida física de la integridad del tracto digestivo superior.
- Patología cardiaca clínicamente significativa (insuficiencia cardiaca congestiva, patología coronaria sintomática) e infarto de miocardio en los últimos 6 meses.
- Pacientes con clínica o sintomatología de neuropatía periférica.
- Rechazo a participar en el estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival |
| Supervivencia global |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Patients will be followed for at least 2 years from randomisation, or death |
| Los pacientes serán seguidos como mínimo 2 años desde la aleatorización, o hasta la muerte |
|
| E.5.2 | Secondary end point(s) |
Quality of life measured with questionnaires QLQ-C30 and QLQ-CR29
Evaluation of prognostic factors.
Costs associated with each treatment.
toxicity
Complications of primary tumor
Complications of surgery
Postoperative Mortality
adverse Events |
Calidad de vida medida con los cuestionarios QLQ-C30 y QLQ-CR29
Evaluación de los factores pronósticos.
Costes asociados a cada tratamiento.
Toxicidad
Complicaciones del tumor primario
Complicaciones de la cirugía
Mortalidad post operatoria
Acontecimientos adversos |
|
| 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 | Yes |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 |
| Resección tumor primario |
| Primary tumor resection |
|
| 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 | 22 |
| 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 | 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
|
| LVLS |
| Última visita del último paciente |
|
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
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