| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Cáncer colorrectal metastásico
(Metastatic colorectal cancer) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052362 |
| E.1.2 | Term | Metastatic colorectal cancer |
|
| 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 |
- Fase 2a
· Determinar la dosis máxima tolerada (DMT) de la lenalidomida en combinación con cetuximab en pacientes con cáncer colorrectal metastásico con K-RAS mutado.
- Fase 2b
· Determinar la tasa de respuesta en los pacientes que padecen cáncer colorrectal metastásico con K-RAS mutado.
(- Phase 2a
To determine the Maximal Tolerated Dose (MTD) of lenalidomide in combination with cetuximab in subjects with KRAS mutant metastatic CRC.
- Phase 2b
To determine the response rate in subjects with KRAS mutant metastatic CRC). |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluar la seguridad y la tolerabilidad en los pacientes que padecen cáncer colorrectal metastásico con K-RAS mutado.
- Evaluar la eficacia clínica en los pacientes que padecen cáncer colorrectal metastásico con K-RAS mutado.
(- To evaluate the safety and tolerability in subjects with KRAS mutant metastatic CRC.
- To assess the clinical efficacy in subjects with KRAS mutant metastatic CRC.) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adenocarcinoma colorrectal metastásico confirmado mediante histología o citología.
2. Una lesión medible unidimensionalmente como mínimo.
3. Tumor con mutación comprobada del gen K-RAS (deben enviarse bloques de tumor en parafina o aproximadamente 25 láminas no teñidas para la prueba de mutación del K-RAS, y el laboratorio central de anatomía patológica debe informar acerca del estado de K-RAS antes de la inclusión en el estudio).
4. Progresión de la enfermedad confirmada mediante imágenes (TAC/RMN) en un plazo de 42 días desde el tratamiento previo.
5. Progresión de la enfermedad con pautas de tratamiento que contienen oxaliplatino -E irinotecán- en el contexto metastásico; al menos una de estas pautas debe contener bevacizumab.
ECOG:
6. Estado funcional según el Eastern Cooperative Oncology Group (ECOG) de <= 1.
Embarazo:
7. Las mujeres en edad fértil deben someterse a análisis de embarazo según la frecuencia descrita en el apartado 21.3 ó 21.4, y los resultados del embarazo deben ser negativos.
8. A menos que se practique la abstinencia completa de relaciones sexuales, las mujeres en edad fértil deben aceptar el uso de métodos anticonceptivos adecuados, tal como se especifica en el apartado 21.3 ó 21.4.
9. Los varones (incluso los que se han sometido a una vasectomía) deben usar un método anticonceptivo de barrera (preservativo) cuando tengan relaciones sexuales con mujeres en edad fértil, tal como se especifica en el apartado 21.3 ó 21.4.
10. Los varones deben estar de acuerdo en no donar semen durante el lapso especificado en el apartado 21.3 ó 21.4.
11. Todos los pacientes deben:
- Entender que el producto en investigación podría tener un riesgo teratogénico.
- Aceptar abstenerse de donar sangre mientras se administra el producto en investigación y tras su suspensión definitiva (véase el apartado 21.3 ó 21.4).
- Aceptar no compartir el medicamento del estudio con otra persona.
- Recibir consejo sobre las precauciones contra el embarazo y los riesgos de la exposición fetal (véase el apartado 21.3 ó 21.4).
Generales:
12. Entender y firmar voluntariamente el documento de consentimiento informado (DCI).
13. Edad >= 18 años en el momento de firmar el consentimiento informado.
14. Ser capaz de cumplir con el calendario de visitas del estudio y otros requisitos del protocolo.
(1.Histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
2.At least one unidimensionally measurable lesion.
3.Documented KRAS mutant tumor (paraffin tumor blocks or approximately 25 unstained slides must be sent for KRAS mutation testing and results reported by central pathology laboratory prior to study enrollment).
4.Imaging confirmed (CT/MRI) disease progression within 42 days of previous treatment.
5.Disease progression on oxaliplatin- AND irinotecan-containing regimens in the metastatic setting, with at least one of these regimens containing bevacizumab.
6.Eastern Cooperative Oncology Group performance status of ? 1.
7.Women of childbearing potential must undergo pregnancy testing based on the frequency outlined in Section 21.3 or 21.4 and pregnancy results must be negative.
8.Unless practicing complete abstinence from heterosexual intercourse, sexually active WCBP must agree to use adequate contraceptive methods as specified in Section 21.3 or 21.4.
9.Males (including those who have had a vasectomy) must use barrier contraception (condom) when engaging in sexual activity with WCBP as specified in Section 21.3 or 21.4.
10.Males must agree not to donate semen or sperm during the duration specified in Section 21.3 or 21.4.
11. All subjects must:
?Understand that the investigational product could have a potential teratogenic risk.
?Agree to abstain from donating blood while taking investigational product and following discontinuation of investigational product (see Section 21.3 or 21.4).
?Agree not to share study medication with another person.
?Be counseled about pregnancy precautions and risks of fetal exposure (see Section 21.3 or 21.4).
12.Understand and voluntarily sign an ICF.
13.Age ? 18 years at the time of signing the ICF.
14.Able to adhere to the study visit schedule and other protocol requirements.) |
|
| E.4 | Principal exclusion criteria |
1. Uso de quimioterapia, hormonoterapia, inmunoterapia o cualquier otro tratamiento para el cáncer o experimental <= 28 días antes del día 1 del primer ciclo.
2. Radioterapia hasta >= 30% de la médula ósea.
3. Intervención quirúrgica <= 28 días antes del día 1 del primer ciclo (están permitidas las intervenciones mínimamente invasivas con fines de diagnóstico o estadiaje de la enfermedad).
4. Tratamiento previo con cetuximab.
5. Tratamiento previo con panitumumab.
6. Tratamiento previo con pomalidomida (CC-4047), lenalidomida o talidomida.
Análisis de laboratorio:
7. Recuento absoluto de neutrófilos (RAN) < 1,5 x 109/l.
8. Recuento de plaquetas < 100 x 109/l.
9. Aclaramiento de creatinina < 50 ml/min (mediante Cockroft- Gault).
10. Bilirrubina > 1,5 x límite superior normal (LSN) (> 2,0 x LSN en presencia del síndrome de Gilbert).
11. Aspartato aminotransferasa sérica (AST) o alanino aminotransferasa (ALT) > 3,0 x LSN (> 5 x LSN en presencia de metástasis hepáticas).
12. Hemoglobina < 9 g/dl.
Otras enfermedades:
13. Metástasis cerebrales sintomáticas no tratadas (no se requieren imágenes craneales).
14. Tromboembolismo venoso <= 6 meses antes del día 1 del primer ciclo.
15. Insuficiencia cardíaca congestiva actual (clases II a IV de la New York Heart Association).
16. Infarto de miocardio <= 12 meses antes del día 1 del primer ciclo.
17. Hipertensión arterial no controlada.
18. Neoplasias malignas en los cinco años previos, con la excepción del carcinoma basocelular o carcinoma espinocelular de la piel o carcinoma “in-situ” de cuello uterino o de mama.
Generales:
19. Cualquier condición (psicológica, sociológica o familiar), incluso la presencia de alteraciones en las pruebas analíticas, que pudieran suponer para el paciente un riesgo inaceptable si éste fuera a participar en un estudio, que pudiera afectar a la correcta interpretación de los datos del estudio, o que impidiera al paciente cumplir con los requisitos del protocolo del estudio.
20. Mujeres embarazadas o en período de lactancia.
(1.Use of chemotherapy, hormonal therapy, immunotherapy, or any other anticancer or experimental therapy ? 28 days prior to Cycle 1 Day
2.Radiotherapy to ? 30% of the bone marrow.
3.Surgery ? 28 days prior to Cycle 1 Day 1 (minimally invasive procedures for the purpose of diagnosis or staging of the disease are permitted).
4.Prior therapy with cetuximab.
5.Prior therapy with panitumumab.
6.Prior therapy with pomalidomide (CC-4047), lenalidomide, or thalidomide.
7.Absolute neutrophil count (ANC) < 1.5 x 109/L.
8.Platelet count < 100 x 109/L.
9.Creatinine Clearance < 50 mL/min (by Cockroft- Gault).
10.Bilirubin > 1.5 x ULN (> 2.0 x ULN in the presence of Gilbert?s Syndrome).
11.Serum AST or ALT > 3.0 x ULN (> 5 x ULN in the presence of liver metastases).
12.Hemoglobin < 9 g/dL.
13.Untreated, symptomatic brain metastases (brain imaging not required).
14.Venous thromboembolism ? 6 months prior to Cycle 1 Day 1.
15.Current congestive heart failure (New York Heart Association class II-IV).
16.Myocardial Infarction (MI) ? 12 months prior to Cycle 1 Day 1.
17.Uncontrolled hypertension.
18.Prior malignancies within 5 years, with the exception of treated basal cell/squamous cell carcinoma of the skin or ?in-situ? carcinoma of the cervix or breast.
19.Any condition (psychological, familial, sociological or geographical), including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study, confound the ability to interpret data from the study, or not allow the subject to comply with the requirements of the study protocol.
20.Pregnant or lactating women. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- Fase 2a
· Dosis máxima tolerada
- Fase 2b
· Tasa de respuesta según los criterios de evaluación de la respuesta en tumores sólidos 1.1 (RECIST 1.1) (Eisenhauer, 2009).
(?Phase 2a
MTD
Phase 2b
Response Rate according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Eisenhauer, 2009). |
|
| 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 | 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
Se incluye en el protocolo
(Provided in the protocol) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| 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 | 5 |
| 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 |
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