E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Resectable Pancreatic Ductal Adenocarcinoma |
Adenocarcinoma ductal pancreático resecable |
|
E.1.1.1 | Medical condition in easily understood language |
pancreatic cancer that can have surgery |
cáncer de páncreas susceptible de ser operado |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033602 |
E.1.2 | Term | Pancreatic adenocarcinoma resectable |
E.1.2 | System Organ Class | 100000004864 |
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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 association of KRAS mutational load and histological tumor response after chemotherapy treatment in patients with PDAC. The histopathological outcome in surgical specimens will be correlated with KRAS mutational load detected in cfDNA of blood by BEAMing |
Evaluar la asociación de la carga mutacional de KRAS y la respuesta tumoral histológica después del tratamiento con quimioterapia en pacientes con PDAC. El resultado histopatológico en muestras quirúrgicas se correlacionará con la carga mutacional de KRAS detectada en cfDNA de sangre por BEAMing. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the association of overall survival and KRAS mutational load after surgery in plasma from patients with PDAC. -To evaluate the association of progression-free survival and KRAS mutational load after surgery in plasma from patients with PDAC. -To evaluate the association of R0 resection rate and KRAS mutational load before surgery in plasma from patients with PDAC. - To evaluate the safety profile of NALIRINOX by recording the incidence of AEs. Acute and late toxicity of NALIRINOX treatment will be evaluated according to the Common Toxicity Criteria (CTC) for adverse events (AE). - To evaluate the efficacy of NALIRINOX in terms of overall survival and one-year survival. |
- Evaluar la asociación de la supervivencia general y la carga mutacional de KRAS después de la cirugía en plasma de pacientes con PDAC. - Evaluar la asociación de la supervivencia libre de progresión y la carga mutacional de KRAS después de la cirugía en plasma de pacientes con PDAC. - Evaluar la asociación de la tasa de resección R0 y la carga mutacional de KRAS antes de la cirugía en plasma de pacientes con PDAC. - Evaluar el perfil de seguridad de NALIRINOX registrando la incidencia de eventos adversos. La toxicidad aguda y tardía del tratamiento con NALIRINOX se evaluará de acuerdo con los Criterios de Toxicidad Comunes (CTC) para los eventos adversos (EA). - Evaluar la eficacia de NALIRINOX en términos de supervivencia global y supervivencia a un año. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or females, aged 18 years or older 2. Histologically or cytologically confirmed diagnosis of PDAC 3. Candidates for pancreatic cancer surgery (no cormobidities that can exclude for surgery) 4. Life expectance of at least 12 months 5. Carbohydrate antigen 19-9 (CA19-9) levels < 500 U/ml 6. ECOG performance status < or 1 7. Adequate bone marrow function 8. Adequate hepatic function 9. Adequate renal function 10. Sexually active men and women of childbearing potential must use efficient contraceptive methods. Contraceptive methods comprise: oral contraceptives, intrauterine devices, sexual abstinence, tubal ligation, IUD, barrier methods or another contraceptive considered appropriate by the investigator. Women of childbearing potential must have a negative serum pregnancy test before study entry. 11. Agree to participate and signed the ICF. |
1. Hombres o mujeres, de 18 años o más 2. Diagnóstico histológico o citológico confirmado de PDAC 3. Candidatos para cirugía de cáncer de páncreas (sin cormobidades que pueden excluir para la cirugía) 4. Esperanza de vida de al menos 12 meses 5. Antígeno de carbohidratos 19-9 (CA19-9) niveles <500 U / ml 6. Estado funcional ECOG < o = 1 7. Adecuada function de médula osea 8. Función hepática adecuada 9. Función renal adecuada 10. Los hombres y mujeres sexualmente activos en edad fértil deben usar métodos anticonceptivos eficientes. Los métodos anticonceptivos comprenden: anticonceptivos orales, dispositivos intrauterinos, abstinencia sexual, ligadura de trompas, DIU, métodos de barrera u otro anticonceptivo que el investigador considere apropiado. Las mujeres en edad fértil deben tener una prueba de embarazo en suero negativa antes del ingreso al estudio. 11. Aceptar participar y firmar el document de consentimiento informado. |
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E.4 | Principal exclusion criteria |
1. Patients with metastatic disease 2. Patients > or =75 years. 3. Uncontrolled coagulopathy 4. Patients with a contraindication to surgery (locally advanced disease or patients not amenable to pancreatic surgery due to a previous comorbidity) 5. Patients with prior or concurrent malignant disease that required treatment with chemotherapy in the past. 6. Previous citotoxic therapy within 36 months for other no-cancer disease (ie arthritis rheumatoid) 7. Known or suspected reactions to any component of the study medication (5-FU/LV, nal- IRI or oxaliplatin) or to components of similar chemical or biologic composition 8. Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule 9. Human immunodeficiency virus (HIV) positivity, active Hepatitis B or Hepatitis C infection. 10. Uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, myocardial infarction, or left ventricular ejection fraction (LVEF) < 50, among others, or psychiatric illness/social situations that would limit compliance with study requirements. 11. Pregnant or breast-feeding women. 12. Any medical condition that, based on investigator’s criteria, places the subject at risk, makes the subject ineligible or may jeopardize protocol compliance. |
1. Pacientes con enfermedad metastásica 2. Pacientes > o = 75 años. 3. Coagulopatía no controlada 4. Pacientes con una contraindicación para la cirugía (enfermedad localmente avanzada o pacientes no susceptibles a cirugía pancreática debido a una comorbilidad previa) 5. Pacientes con enfermedad maligna previa o concurrente que requirieron tratamiento con quimioterapia en el pasado. 6. Terapia antitumoral previa en los 36 meses previos 7. Reacciones conocidas o sospechadas de cualquier componente de la medicación del estudio (5-FU / LV, nal-IRI u oxaliplatino) o a componentes de composición química o biológica similar 8. Participación concurrente en cualquier otro ensayo clínico que pueda interferir con el programa terapéutico 9. Positividad del virus de la inmunodeficiencia humana (VIH), hepatitis B activa o infección de la hepatitis C. 10. Enfermedad no controlada, incluyendo infección activa o en curso, insuficiencia cardíaca congestiva sintomática, angina inestable, arritmia cardíaca, infarto de miocardio o fracción de eyección del ventrículo izquierdo (FEVI) <50, entre otros, o enfermedades psiquiátricas / situaciones sociales que limitarían el cumplimiento de los requisitos del estudio . 11. Mujeres embarazadas o lactantes. 12. Cualquier condición médica que, de acuerdo con los criterios del investigador, ponga al sujeto en riesgo, lo haga inelegible o ponga en riesgo el cumplimiento del protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with a good histological tumour response in the resected specimens after neoadjuvant chemotherapy with NALIRINOX and surgical removal according to the Ryan’s classification in a dichotomic way (0-1: good; 2-3: bad) in KRAS positive and negative patients assessed by liquid biopsy and BEAMing. |
Proporción de sujetos con una buena respuesta histológica tumoral en las muestras resecadas después de la quimioterapia neoadyuvante con NALIRINOX y la extirpación quirúrgica de acuerdo con la clasSiicación de Ryan de forma dicotómica (0-1: bueno; 2-3: malo) en pacientes KRAS positivos y negativos evaluados por biopsia líquida y BEAMing. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
8 weeks after surgical intervention |
8 semanas tras la intervención quirúrgica |
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E.5.2 | Secondary end point(s) |
- R0 resection, PFS, 1-year survival and OS in baseline KRAS+ and KRAS- subjects. - Assessment of the number and proportion of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX and its impact on R0 resection, histological tumour response, PFS and 1-year survival and OS. - Description of the safety profile of the neoadjuvant NALIRINOX scheme: AEs, SAEs according to the CTCAE. |
- resección R0, PFS, supervivencia a 1 año y SG en sujetos KRAS y KRAS iniciales. - Evaluación del número y la proporción de sujetos con KRAS que cambian a KRAS + (y de KRAS + a negativo) después del neoadyuvante NALIRINOX y su impacto en la resección R0, la respuesta tumoral histológica, la SLP y la supervivencia a 1 año y la SG. - Descripción del perfil de seguridad del esquema neoadyuvante NALIRINOX: AEs, SAEs según CTCAE. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Through the study |
A lo largo del estudio |
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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 | Yes |
E.6.4 | Safety | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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 | 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
|
Last Subject Last Visit |
Última visita del último paciente |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |