E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic colorectal cancer |
Cancer colorectal metastásico |
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E.1.1.1 | Medical condition in easily understood language |
Colorectal cancer |
Cancer colorectal |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To evaluate the progression-free survival (PFS) in patients receiving S 95005 + bevacizumab (experimental arm) or capecitabine + bevacizumab (control arm) as first-line treatment for metastatic colorectal cancer in patients non-eligible for intensive therapy. |
Evaluar la supervivencia libre de progresión (SLP) en pacientes que reciban S95005+ bevacizumab (brazo experimental) ó capecitabina +bevacizumab (brazo control) como primera línea de tratamiento para el cancer colorectal metastásico en pacientes que no son candidatos para una terapia intensiva. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the overall response rate (ORR), duration of response (DR), disease control rate (DCR), overall survival (OS), safety and tolerability, quality of life (QoL) in patients receiving S 95005 + bevacizumab (experimental arm) or capecitabine + bevacizumab (control arm) as first-line treatment for metastatic colorectal cancer in patients non-eligible for intensive therapy. Exploratory: Evaluate the biomarkers potentially predictive of response and resistance to S 95005 given in combination using blood samples and archived tumour biopsy (if available). |
Evaluar la Tasa de respuesta global (TRG), duración de la respuesta (DR), tasa de control de la enfermedad (TCE), supervivencia global (SG) ,tolerabilidad y seguridad, calidad de vida en pacientes que reciban S95005+ bevacizumab (brazo experimental) ó capecitabina +bevacizumab (brazo control) como primera línea de tratamiento para el cancer colorectal metastásico en pacientes que no son candidatos para una terapia intensiva. Exploratorio: Evaluar los biomarcadores potencialmente predictivos de respuesta y resistencia a S 95005 dado en combinación, utilizando muestras de sangre y biopsias tumorales archivadas (si están disponibles). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent obtained. - Male or Female participant aged ?18 years old. - Has ECOG performance status of 0, 1 or 2 at the time of the randomisation. - Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum. - RAS status must have been determined (mutant or wild). - Has at least one measurable metastatic lesion. - No previous anticancer therapy for metastatic colorectal cancer. - Previous adjuvant (or neoadjuvant for patients with rectal cancer) chemotherapy is allowed only if if it has been completed more than 6 months before start of study treatment. - In the judgment of the Investigator, patient is not a candidate for combination chemotherapy with irinotecan or oxaliplatin, or for curative resection of metastatic lesions. - Is able to take medication orally (i.e., no feeding tube). - Has adequate organ function. - Coagulation parameters in normal limit. - Women of childbearing potential must have been tested negative in a serum pregnancy test. Male and female patients who have the potential to reproduce must agree to use a highly effective method of birth control. - Is willing and able to comply with scheduled visits and study procedures. |
-Obtener el consentimiento informado por escrito -Paciente hombre o mujer de ? 18 años. -Estado funcional ECOG de 0, 1 o 2 en el momento de la aleatorización -Adenocarcinoma de colon o recto histológica o citológicamente confirmado. -Estado del biomarcador RAS determinado (mutado o salvaje). -Presentar, como mínimo, una lesión metastásica medible - No terapia antineoplásica previa para el cáncer colorrectal metastásico. - Sólo se permite quimioterapia adyuvante previa (o neoadyuvante para pacientes con cáncer rectal) si ha transcurrido más de 6 meses desde su finalización y el inicio de la medicación del estudio. -Según la opinión del investigador, el paciente no es candidato para la quimioterapia combinada con irinotecán u oxaliplatino. -Capacidad de tomar el medicamento por vía oral(es decir, sin sonda nasogástrica). -Adecuada función orgánica -Parámetros de la coagulación dentro de los limtes de normalidad -Las mujeres en edad fértil deben haber obtenido un resultado negativo en la prueba de embarazo en suero . Los pacientes hombres y mujeres que estén en edad fertil deben aceptar el uso de un método anticonceptivo altamente eficaz . -Está dispuesto y puede cumplir con las visitas programadas y los procedimientos del estudio. |
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E.4 | Principal exclusion criteria |
- Foreseeable poor compliance to the study procedures. - Is a pregnant or lactating female. - Is inappropriate for entry into this study in the judgment of the Investigator. - Has certain serious illness or serious medical condition(s) described in the protocol. - Has had certain other recent treatment e.g. major surgery, field radiation, received investigational agent, within the specified time frames prior to study drug administration. - Has previously received S 95005 or history of allergic reactions attributed to compounds of similar or biologic composition to S 95005. |
-Bajo cumplimiento predecible de los procedimientos del estudio. -Mujer embarazada o lactante. -No es adecuada su inclusión en este estudio según la opinión del investigador. -Presenta una enfermedad grave o una condición médica grave descrita en el protocolo. -Haber tenidociertos tratamientos como por ejemplo: cirugia mayor, radiación de campo, haber recibido agentes en investigación, durante el periodo de tratamiento previo a la administración de la medicación del estudio. -Haber recibido previamente s95005 ó antecedentes de reacciones alérgicas a compuestos de composición biológica similar a la del S95005. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) |
Supervicencia libre de progresión |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumour measurements within 28 days prior to Day 1 of Cycle 1 and every 8 weeks thereafter. |
Evaluaciones tumorales en los 28 días previos al día 1 del ciclo 1 y posteriormente cada 8 semanas. |
|
E.5.2 | Secondary end point(s) |
- Overall Response Rate (ORR). - Duration of Response (DR) - Disease control rate (DCR) - Overall Survival - Safety and tolerability assessed by: ? Incidence of Adverse Events (AE). ? Laboratory tests: haematology, blood biochemistry, coagulation, urinalysis. ? Physical examination and performance status (ECOG). ? Vital signs: blood pressure (BP), heart rate (HR), body temperature, respiration rate, body weight. ? 12-leads ECG parameters. - Quality of Life assessed by a quality of life questionnaire. - Exploratory endpoints:Biomarkers using blood samples and archived tumour biopsy (if available). |
- Tasa de respuesta global (TRG) - Duración de la respuesta (DR) - Tasa de control de la enfermedad (TCE) - Supervivencia global (SG) - Tolerabilidad y seguridad evaluada mediante: -Incidencia de Acontecimeintos Adversos -Pruebas de laboratorio: hematología, bioquímica en sangre, coagulación y urianálisis. -Exploración física y estado funcional (ECOG) -Constantes vitales: presión arterial (PA), frecuencia cardíaca (FC), temperatura corporal, frecuencia respiratoria y peso corporal. ? -ECG de 12 derivaciones. -Calidad de vida evaluada mediante cuestionarios de calidad de vida. -Criterios exploratorios de valoración: Biomarcadores utilizando muestras de sangre y biopsias tumorales archivadas (si están disponibles). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ORR, DR, DCR: tumour measurements within 28 days prior to Day 1 of Cycle 1 and every 8 weeks thereafter. - Overall Survival: survival status obtained at scheduled 8-week intervals until patient death or until 100 PFS events are reached and the final analysis has been performed. - Adverse Events: all over the study. - Laboratory tests, physical exam, ECOG, vital signs: within 5 days prior randomisation, within 3 days prior C1D1, C1D15 (except for coagulation, physical exam, ECOG), Day 1 of subsequent cycles, Day 15 of subsequent cycles (only for vital signs), withdrawal visit. - Quality of life assessments: every 12 weeks. - Biomarkers measurements: blood samples collected at C1D1 and withdrawal visit. |
TRG, DR y TCE: evaluaciones tumorales en los 28 días previos C1D1 y luego cada 8 semanas. SG: estado de supervivencia obtenido cada 8 semanas hasta que el paciente fallezca ó hasta que se alcancen 100 acontecimientos de supervivencia libre de progresión y se haya realizado el análisis final. AA: a lo largo de todo el estudio. Pruebas de laboratorio, exploración física, ECOG, constantes vitales: en los 5 días previos a la aleatorización , en los 3 días previos a C1D1, C1D15 (excepto coagulación, exploración física y el ECOG) en el D1 de los siguientes ciclos , en el D15 de los siguientes ciclos sólo constantes vitales), en la visita de retirada. Evaluaciones de Q de V: cada 12 sem mediciones de biomarcadores: muestras sangre recogidas en C1D1 y en la visita de retirada. |
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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 | No |
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 | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Capecitabina |
Capecitabine |
|
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
Russian Federation |
Spain |
United Kingdom |
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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
|
LVLS |
Ultima visita del ultimo 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 | 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 |