E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic colorectal cancer |
Cancer metastásico colorectal |
|
E.1.1.1 | Medical condition in easily understood language |
metastatic colorectal cancer |
Cancer metastásico colorectal |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05] |
MedDRA Classification |
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 determine the 6 month PFS (Progression Free Survival) benefit of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated metastatic colorectal cancer (mCRC). |
Determinar la supervivencia libre de progresión de 6 meses de cetuximab solo o en combinación con irinotecan en pacientes con cáncer colorectal metastásico con KRAS salvaje o KRAS mutado en C13D |
|
E.2.2 | Secondary objectives of the trial |
- To determine the response rate in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan - To determine the overall survival in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan - To evaluate Quality of Life using the FACT-C, DLQI and FACT-EGFRI 18 questionnaires. |
*Determinar la tasa de respuesta en pacientes con cáncer colorectal metastásico con KRAS salvaje o KRAS mutado en C13D tratados con cetuximab solo o en combinación con irinotecan (respuesta completa o parcial definida por los criterios RECIST versión 1.1) *Determinar la supervivencia global en pacientes con cáncer colorectal metastásico con KRAS salvaje o KRAS mutado en C13D tratados con cetuximab solo o en combinación con irinotecan (muerte por cualquier causa) *Evaluar la Calidad de Vida (definida por los peores valores de FACT-C, DLQI y FACT-EGFRI 18). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females with histologically confirmed colorectal cancer; 2. Age more than 18 yrs; 3. Metastatic disease not amenable to complete resection; 4. Measurable or evaluable disease as assessed by CT scan of the chest, abdomen and pelvis as per the RECIST v1.1 criteria; 5. Prior confirmation of tumour KRAS status as either KRAS WT (with no mutations or changes in BRAF, NRAS, PIK3CA exon20) OR KRAS G13D mutation, 6. ECOG performance status of 0-2; 7. Received and progressed on, or intolerant of all therapies listed below: (failure is defined as radiological progression during therapy, or toxicity limiting further therapy, or progression within 6 months of adjuvant treatment) - thymidylate synthase inhibitor - irinotecan-containing regimen - oxaliplatin-containing regimen, OR have documented unsuitability for an oxaliplatin-containing regimen; 8. Adequate haematological and renal function; 9. Adequate liver function; 10. Life expectancy of at least 12 weeks; 11. Study treatment both planned and able to start within 14 days of randomisation; 12. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments; 13. Signed, written informed consent |
- Hombres y mujeres con confirmación de cancer colorectal histológicamente. - Mayores de 18 años -Cancer metastásico no susceptible de completar la resección. - Enfermedad mensurable o evaluable como evaluado por exploración de CT escaner del pecho, abdomen y pelvis según criterios RECIST v1.1 -Confirmación previa de tumor KRAS estado como PESO KRAS (sin mutaciones o como cambios de BRAF, NRAS, PIK3CA exon20) ó KRAS G13D mutación. ECOG estatus de 0 a 2 -Ha recibido y progresó sobre, o intolerante de todas las terapias catalogadas debajo: (el fracaso es definido como la progresión radiológica durante la terapia, o la toxicidad que limita dicha terapia, o la progresión 6 meses antes del tratamiento adyuvante) - thymidylate synthase el inhibidor - el irinotecan-conteniendo del régimen - el oxaliplatin-conteniendo del régimen, o ha documentado la inconveniencia para un tratamiento que contiene oxaliplatino. -Esperanza de vida de al menos 12 semanas. -Consentimiento informado firmado |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with cetuximab or other drugs targeting the EGFR pathway; 2. Severe restrictive lung disease or radiological pulmonary findings; 3. Brain metastases that are either untreated, symptomatic, or which have not been stable for at least one month after treatment; 4. History of another malignancy within 5 years prior to registration (exception of treated cervical carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder) 5. Severe or uncontrolled cardiovascular disease; 6. Concurrent illness; 7. Presence of any psychological, familial, sociological or geographical condition; 8. Pregnancy, lactation, or inadequate contraception. |
-Tratamiento previo con cetuximab u otras medicinas que apuntan el sendero EGFR. - Enfermedad severa restrictiva pulmonar o hallazgos radiológicas pulmonares. - La metástasis cerebral no tratada, sintomática, o que no ha sido estable para al menos un mes después del tratamiento. -Historia de otra malignidad dentro de 5 años antes de registro. - Problemas cardiovasculares severos o no controlados. -Embarazo, estado de lactancia o no control de la contracepción. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To determine the 6 month Progression Free Survival (PFS) benefit of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated colorectal cancer (mCRC) (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1). |
Determninar a los 6 meses la supervivencia libre de progresión debida a Cetuximab en monoterapia o en combinación con Irinotecan en pacientes con KRAS WT or KRAS G13D en cancer colorectal. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of study |
Final del estudio. |
|
E.5.2 | Secondary end point(s) |
- To determine the response rate in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan (Complete and Partial Responses as defined by RECIST criteria version 1.1). - To determine the overall survival in patients with KRAS WT or KRAS G13D mutated mCRC treated with cetuximab alone or in combination with irinotecan (Death from any cause). - To evaluate Quality of Life (as defined by worse scores on FACT-C, DLQI and FACT-EGFRI 18) |
-Determinar la tasa de respuesta en pacientes con cáncer colorectal metastásico con KRAS salvaje o KRAS mutado en C13D tratados con cetuximab solo o en combinación con irinotecan (respuesta completa o parcial definida por los criterios RECIST versión 1.1) -Determinar la supervivencia global en pacientes con cáncer colorectal metastásico con KRAS salvaje o KRAS mutado en C13D tratados con cetuximab solo o en combinación con irinotecan (muerte por cualquier causa) -Evaluar la Calidad de Vida (definida por los peores valores de FACT-C, DLQI y FACT-EGFRI 18). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Final del estudio |
|
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 | Yes |
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 | 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 | 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
| 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 | 2 |
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 |
Spain |
United Kingdom |
|
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,ie. At the latest 1 year from randomisation of last patient |
LVLS En el ultimo año desde la aleatorización del último paciente. |
|
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 | 29 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |