| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Colorectal cancer patients with metastatic disease limited to the liver with poor prognostic criteria. |
| Pacientes con cáncer colorrectal y enfermedad metastásica limitada al hígado con criterios de mal pronóstico. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Colorectal cancer patients with metastasis limited to the liver |
| Pacientes con cáncer colorrectal con metastasis limitadas al hígado |
|
| 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 | 27.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052362 |
| E.1.2 | Term | Metastatic colorectal cancer |
| 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 |
Efficacy:
Evaluate the radiological objective response rate according to the RECIST version 1.1 criteria at 6 months. |
Eficacia:
Evaluar la tasa de respuesta objetiva radiológica según los criterios RECIST versión 1.1 a los 6 meses. |
|
| E.2.2 | Secondary objectives of the trial |
Assess overall survival.
Assess progression-free survival (PFS).
Assess the safety profile
Evaluate hepatic PFS.
Evaluate R0 liver surgery rate |
Evaluar la supervivencia global.
Evaluar la supervivencia libre de progresión (SLP).
Evaluar el perfil de seguridad
Evaluar SLP hepática.
Evaluar la tasa de cirugía hepática R0 |
|
| 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 |
| Serum tumor biomarkers using blood biological samples |
| Marcadores tumorales séricos utilizando muestras biológicas de sangre |
|
| E.3 | Principal inclusion criteria |
1. Patients aged ≥ 18 years.
2. Patients with colorectal cancer and exclusive liver metastases with poor prognostic criteria,> 3 lesions and / or size> 5 cm. Patients with the diagnosis of liver metastases with synchronous presentation or with a disease-free interval may be included. If the primary tumor has not been resected, it must be clinically stable.
3. Measurable disease following RECIST version 1.1 criteria
4. Adequate bone marrow function, according to:
Hemoglobin ≥ 9.0 g / dl (patients with hemoglobin <9 g / dl can be transfused before inclusion in the study
Platelet count ≥ 100 x 109 / L
Absolute Neutrophil Count (ANC) ≥ 1.5x 109 / L
5. Adequate liver function, according to:
Serum bilirubin ≤ 1.5 x the upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
Alkaline phosphatase ≤ 5 x ULN
Adequate renal function, with creatinine levels <1.5 mg / dL. BUN< 50 mg / dl or blood UREA < 18 mmol/L.
Albumin> 3.0 g / dL
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
7. Patients capable of understanding the information and giving their written informed consent to participate in the study
8. Women and men of childbearing potential must commit to abstinence from sex or use barrier contraception during the study and must have a negative pregnancy test. |
1. Pacientes con edad ≥ 18 años.
2. Pacientes con cáncer colorrectal y metástasis hepáticas exclusivas con criterios de mal pronóstico, >3 lesiones y/o tamaño >5 cm. Se podrán incluir pacientes con el diagnóstico de las metástasis hepáticas de presentación sincrónica o con un intervalo libre de enfermedad. Si el tumor primario no se ha resecado, debe estar clínicamente estable.
3. Enfermedad medible siguiendo los criterios RECIST versión 1.1
4. Adecuada función de la médula ósea, según:
Hemoglobina ≥ 9,0 g/dl (pacientes con hemoglobina < 9 g/dl pueden transfundirse antes de la inclusión en el estudio
Recuento de plaquetas ≥ 100 x 109/L
Recuento absoluto de neutrófilos (RAN) ≥ 1.5x 109/L
5. Adecuada función hepática, según:
Bilirrubina sérica ≤ 1.5 x el límite superior de la normalidad (LSN)
Alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST) ≤ 5 x LSN.
Fosfatasa alcalina ≤ 5 x LSN
Adecuada función renal, con niveles de creatinina < 1,5 mg/dL. BUN< 50 md/dl o UREA en sangre < 18 mmol/L.
Albúmina >3.0 g/dL
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
7. Pacientes capaces de comprender la información y de otorgar su consentimiento informado por escrito para participar en el estudio
8. Las mujeres y hombres en edad fértil deben comprometerse a la abstinencia sexual o a la utilización de métodos anticonceptivos de barrera durante el estudio y deben tener un test de embarazo negativo. |
|
| E.4 | Principal exclusion criteria |
1. Extension of the disease> 50% of the liver parenchyma (evaluated by CT performed within the month prior to inclusion)
2. Patients with liver metastases measuring less than 5 cm or with a total of 3 or fewer lesions.
3. Previous chemotherapy treatment for metastatic colorectal cancer
4. Clinically significant cardiovascular diseases: cerebrovascular accident / stroke (≤ 6 months before inclusion in the trial), myocardial infarction (≤ 6 months before inclusion in the trial), unstable angina, uncontrolled hypertension, congestive heart failure of NYHA grade II or higher or severe cardiac arrhythmia.
5. History of malignancy in the last three years, except for basal cell carcinoma of the skin or carcinoma in situ of the cervix treated appropriately.
6. Altered coagulation (Quick> 50%)
7. Patients with active infectious processes
8. Patients with any of the contraindications specified in the technical data sheet of the study drug or with allergies to some of the drugs used
8. Pregnant or lactating patients
10. Portal thrombosis
11. Severe portal hypertension
12. Extrahepatic metastases |
1. Extensión de la enfermedad > 50% del parénquima hepático (evaluado por TC realizado dentro del mes previo a su inclusión)
2. Pacientes con metástasis hepática que midan menos de 5 cm o sumen en total 3 o menos lesiones.
3. Tratamiento quimioterápico previo para cáncer colorrectal metastásico
4. Enfermedades cardiovasculares clínicamente significativas: accidente cerebrovascular/ictus (≤ 6 meses antes de la inclusión en el ensayo), infarto de miocardio (≤ 6 meses antes de la inclusión en el ensayo), angina inestable, hipertensión arterial no controlada, insuficiencia cardíaca congestiva de grado II o superior de la NYHA o arritmia cardíaca grave.
5. Historia de malignidad en los últimos tres años, excepto el carcinoma de células basales de la piel o carcinoma in situ del cuello del útero tratados adecuadamente.
6. Coagulación alterada (Quick >50%)
7. Pacientes con procesos infecciosos activos
8. Pacientes que presenten alguna de las contraindicaciones especificadas en la ficha técnica del fármaco en estudio o con alergias a algunos de los fármacos empleados
9. Pacientes embarazadas o en periodo de lactancia
10. Trombosis portal
11. Hipertensión portal severa
12. Metástasis extrahepáticas |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients with an objective radiological response rate at 6 months of treatment. Objective response rate is understood as the proportion of patients with reduced tumor size according to RECIST 1.1 criteria. |
| Proporción de pacientes que presentan tasa de respuesta objetiva radiológica a los 6 meses de tratamiento. Se entiende por tasa de respuesta objetiva la proporción de pacientes con reducción del tamaño tumoral según criterios RECIST 1.1. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Overall survival time. Overall survival is understood as the time elapsed from the inclusion of the patient in the study to the date of death from any cause.
2. Progression-free survival time. PFS is understood as the time elapsed from the inclusion of the patient in the study to the date of radiological progression or death. Patients without radiological documentation of progression will be censored on the date of the last control without evidence of progression.
3. Proportion of patients with clinical adverse events, laboratory abnormalities and proportion of patients with discontinuation of treatment due to toxicity or intolerance.
4. Hepatic PFS: time from patient inclusion in the study to liver radiological progression according to RECIST 1.1 criteria.
5. Proportion of patients undergoing R0 surgery for liver metastases |
1. Tiempo de supervivencia global. Se entiende por supervivencia global como el tiempo transcurrido desde la inclusión del paciente en el estudio hasta la fecha de la muerte por cualquier causa.
2. Tiempo de supervivencia libre de progresión. Se entiende por SLP como el tiempo transcurrido desde la inclusión del paciente en el estudio hasta la fecha de progresión radiológica o muerte. Los pacientes sin documentación radiológica de progresión se censurarán en la fecha del último control sin evidencia de progresión.
3. Proporción de pacientes con acontecimientos adversos clínicos, alteraciones de laboratorio y proporción de pacientes con discontinuación de tratamiento por toxicidad o intolerancia.
4. SLP hepática: tiempo desde la inclusión del paciente en el estudio hasta la progresión radiológica a nivel hepático según criterios RECIST 1.1.
5. Proporción de pacientes en los que se realiza cirugía R0 de las metástasis hepáticas. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Through the study up to 24 months |
| Durante el estudio, hasta 24 meses |
|
| 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 | 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 |
| Atención estándar (FOLFOX más un Ab monoclonal (bevacizumab, cetuximab o panitumumab) |
| Standard of care (FOLFOX plus a monoclonal Ab (bevacizumab, cetuximab or panitumumab) |
|
| 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 | 9 |
| 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
|
| The end of the study will coincide with the last follow-up visit of the last patient included in the study. |
| La finalización del estudio coincidirá con la última visita de seguimiento del último paciente incluido en el estudio |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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