E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory metastatic colorectal cancer |
Cancer colorrectal metastásico refractario |
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E.1.1.1 | Medical condition in easily understood language |
Colorrectal cancer |
Cáncer de colon y recto |
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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 | 14.1 |
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 compare the following endpoints for the TAS-102 (experimental) arm with the placebo (control) arm in patients with refractory metastatic colorectal cancer: Overall survival (OS) |
Comparar los siguientes eventos del brazo de TAS-102 (medicación experimental) con el brazo placebo (control) en pacientes con cáncer colorrectal metastásico refractario: Supervivencia Global (SG) |
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E.2.2 | Secondary objectives of the trial |
To compare the following endpoints for the TAS-102 (experimental) arm with the placebo (control) arm in patients with refractory metastatic colorectal cancer: Progression-free survival (PFS) Safety and tolerability Time to treatment failure (TTF) Overall response rate (ORR) Disease control rate (DCR) Duration of response (DR) Subgroup analysis by KRAS status on OS and PFS |
Compara los siguientes eventos del brazo de TAS-102 (experimental) con el brazo placebo (control) en pacientes con cáncer colorrectal metastásico refractario: Supervivencia Libre de Progresión (SLP) Seguridad y Tolerabilidad Tiempo hasta Fallo de Tratamiento (TTF) Tasa de Respuesta Global (TRG) Tasa de Control de la Enfermedad (TCE) Duración de la Respuesta (DR) Análisis de SG y SLP en los subgrupos según KRAS |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study: -Has provided written informed consent -Be at least 18 years old -Has histologically or cytologically confirmed adenocarcinoma of the colon or rectum -Has received at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer and is refractory to or failing those chemotherapies. -ECOG performance status of 0 or 1 -Is able to take medications orally -Has adequate organ function (bone marrow, kidney and liver) -Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control |
El paciente debe cumplir todos los siguientes criterios de inclusión para ser elegible de participar en el estudio: -Haber firmado el consentimiento informado -Tener al menos 18 años de edad -Estar diagnosticados histológica o citológicamente de adenocarcinoma de colon o de recto -Haber recibido al menos 2 regimenes de quimioterapia convencional para cancer colorrectar metastásico y ser refractorio o haber fallado a dichas quimioterapias -ECOG de 0 a 1 -Ser capaz de tomar medicación oral -Tener una adecuada función orgánica (médula ósea, riñón e hígado) -Mujeres en edad fértil deben tener un test de embarazo negativo realizado en los 7 días anteriores a la randomización -Tener voluntad y ser capaz de cumplir con las visitas programadas y los procedimientos del estudio |
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E.4 | Principal exclusion criteria |
Exclusion Criteria: 1. Certain serious illnesses or medical condition(s) 2. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration. 3. Has received TAS-102. 4.Has unresolved toxicity to less than or equal to CTCAE Grade 1 attributed to any prior therapies 5. Is a pregnant or lactating female. 6. Is inappropriate for entry into this study in the judgment of the Investigator. |
1. Tener una enfermedad seria o una condición (es) médica (s) 2. Haber sido tratado recientemente con cirugía mayor, terapia anticancerígena, radioterapia de campo extendido o limitado, o cualquier producto en investigación. 3. Haber recibido TAS-102. 4. Tener alguna toxicidad no resuelta a menos de o igual a Grado 1 según CTCAE atribuida a cualquiera de las terapias anteriores. 5. Estar embarazada o en fase de lactancia. 6. No ser apto para entrar en el estudio a opinión del investigador. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Survival is the primary endpoint of this study and is defined as the time (in months) from the date of randomization to the death date. In the absence of death confirmation or for patients alive as of the OS cut-off date, survival time will be censored at the date of last study follow-up, or the cut-off date, whichever is earlier. |
Supervivencia es el criterio de evaluación principal del estudio y se define como el tiempo (en meses) desde la fecha de randomización hasta la fecha de la muerte. En ausencia de confirmación de muerte o en pacientes vivos a fecha del corte de base de datos, el tiempo de supervivencia será aquel de a última fecha de seguimiento, o la fecha del cierre de base de datos, lo que antes tenga lugar. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later. |
Cada 8 semanas. El estado de supervivencia se recogerá hasta 12 meses después de la randomización del último paciente o hasta que se alcance el número de eventos requeridos (muertes), lo que ocurra más tarde. |
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E.5.2 | Secondary end point(s) |
To compare the Progression-Free-Survival (PFS) for TAS-102 (experimental arm) with placebo (control arm) in patients with refractory metastatic colorectal cancer. To assess the safety and tolerability for TAS-102 (experimental arm) in patients with refractory metastatic colorectal cancer. |
Para comparar el tiempo libre de progresión (SLP) de TAS-102 (brazo experimental) con placebo (brazo control) en pacientes con cáncer colorrectar metastásico refractario. Evaluar la seguridad y tolerabilidad de TAS-102 (brazo experimental) en pacientes con cáncer colorrectar metastásico refractario. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 8 weeks. Tumor assessments will be performed until the patients develops radiologic progression or until the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later. Safety and tolerabiltity will be assessed until 30 days following last administration of study medication or until initiation of new anticancer treatment. |
Cada 8 semanas. Las evaluaciones de los tumores de los apcientes hasta la progresión o hasta el inicio de una nueva terapia anticancerígena hasta 12 meses de que el ultimo paciente hasya sido randomizado o hasta que se haya alcanzaod el numero de eventos (muertes), lo que antes ocurra. La seguridad y tolerabilidad se seguirán hasta 30 dias después de la ultima administración de la medicación o hasta que se inicie una nueva terapia anticancerigena. |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Japan |
United States |
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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
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12 months after the first dose of study medication for the last patient randomized or until the target number of events (deaths) is met, whichever is later. |
12 meses después de la primera dosis del último paciente randomizado o hasta que se alcance el número de eventos (muertes) descritos, lo que ocurra más tarde. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |