| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| pancreatic cancer |
| cáncer de páncreas |
|
| E.1.1.1 | Medical condition in easily understood language |
| pancreatic cancer |
| cáncer de páncreas |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| 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 |
Run in phase: Dose limiting toxicity (DLT) and Maximal tolerated dose (MTD) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer.
Phase II part: Efficacy between the treatment arms in terms of progression free survival. |
Fase de rodaje: Dosis de toxicidad limitante (DLT) y la máxima dosis tolerada (MTF) de naI-IRI cuando se co-administra con dosis fija de S1 en pacientes con cáncer de páncreas metastásico.
Parte de la fase 2: eficacia entre los brazos de tratamiento en términos de supervivencia libre de progresión. |
|
| E.2.2 | Secondary objectives of the trial |
Overall survival
Response rate according to RECIST 1.1
Adverse events according to NCI CTC version 4.0
Quality of life |
Supervivencia global
Tasa de respuesta de acuerdo a RECIST 1.1
Acontecimientos adversos de acuerdo a NCI CTC versión 4.0
Calidad de vida |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Able to understand and provide written informed consent
2. ≥ 18 years of age
3. Histologically or cytologically confirmed adenocarcinoma of pancreas
4. Documented metastatic disease, according to RECIST 1.1.
5. Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine based treatment
6. Adequate hepatic, renal and hematological function |
1. Capaz de entender y proporcionar consentimiento informado por escrito
2. ≥ 18 años
3. Adenocarcinoma de páncreas exocrino confirmado histológicamente o citológicamente
4. Enfermedad metastásica documentada, de acuerdo a RECIST 1.1.
5. Previamente tratado con gemcitabina o terapia que contiene gemcitabina, o progresión dentro de los 6 meses posteriores al tratamiento adyuvante con gemcitabina
6. Función hepática, renal y hematológica adecuada. |
|
| E.4 | Principal exclusion criteria |
Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)
2. Severe renal impairment (CLcr ≤ 30 ml/min)
3. Inadequate bone marrow reserves as evidenced by:
a. ANC ≤ 1,5 x 10 9 /L; or
b. Platelet count ≤ 100 x 10 9 /L;
4. WHO/PS 2 or higher
Any clinically significant disorder impacting the risk-benefit balance negatively per physician’s judgment
6. Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
7. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
8. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
9. Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician’s opinion might compromise the patient’s health
10. Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
11. Known hypersensitivity to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
12. Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
13. Previous treatment with fluoropyrimidine therapy
14. Known dihydropyrimidine dehydrogenase (DPD) deficiency
15. Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of liposomal irinotecan (Nal-IRI).
16. Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine. |
1. Bilirrubina total en suero ≥1.5 x ULN (se permite el drenaje biliar por obstrucción biliar).
2. Insuficiencia renal grave (CLcr ≤ 30 ml / min)
3. Reservas inadecuadas de médula ósea como lo demuestran:
a. ANC ≤ 1,5 x 10 9 / L; o
b.Recuento de plaquetas ≤ 100 x 109 / L
4. WHO/PS 2 o mayor.
5. Cualquier trastorno clínicamente significativo que afecte negativamente el equilibrio riesgo-beneficio según el criterio del médico.
6. Cualquier trastorno gastrointestinal clínicamente significativo, incluidos trastornos hepáticos, sangrado, inflamación, oclusión o diarrea> grado 1
7. Eventos tromboembólicos arteriales severos (infarto de miocardio, angina de pecho inestable, accidente cerebrovascular) en los últimos 6 meses
8. Insuficiencia cardíaca congestiva de clase III o IV de NYHA, arritmias ventriculares o presión arterial no controlada. ECG anormal conocido con hallazgos anormales clínicamente significativos
9. Infección activa o fiebre inexplicable> 38.5 ° C (excluyendo fiebre tumoral), que en opinión del médico podría comprometer la salud del paciente.
10. Uso actual o cualquier uso en las últimas dos semanas de inductores / inhibidores fuertes de la enzima CYP3A y / o inhibidores de UGT1A fuertes
11. Hipersensibilidad conocida a cualquiera de los componentes del irinotecan liposomal (nal-IRI), otras formulaciones de irinotecan liposomal, irinotecan, fluoropirimidinas o leucovorina.
12. Hipersensibilidad a cualquiera de los principios activos (tegafur, gimeracilo y oteracilo)
13. Tratamiento previo con terapia con fluoropirimidina.
14. Deficiencia conocida de dihidropirimidina deshidrogenasa (DPD)
15. Lactancia, embarazo conocido, prueba de embarazo en suero positiva o falta de voluntad para utilizar un método anticonceptivo confiable, durante la terapia y durante 3 meses después de la última dosis de irinotecán liposomal (IRN-nal).
16. Tratamiento dentro de las 4 semanas con inhibidores de DPD, incluyendo sorivudina o sus análogos químicamente relacionados como la brivudina |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Run in phase: Dose limiting toxicity (DLT) and Maximal tolerated dose (MTD) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer.
Phase II part: Efficacy between the treatment arms in terms of progression free survival. |
Fase de rodaje: Dosis de toxicidad limitante (DLT) y la máxima dosis tolerada (MTF) de naI-IRI cuando se co-administra con dosis fija de S1 en pacientes con cáncer de páncreas metastásico.
Parte de la fase 2: eficacia entre los brazos de tratamiento en términos de supervivencia libre de progresión. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Evaluation with CTscan/ MRI will take place every 2 months |
| La evaluación con CTscan/ MRI se realizará cada 2 meses. |
|
| E.5.2 | Secondary end point(s) |
Overall survival
Response rate according to RECIST 1.1
Adverse events according to NCI CTC version 4.0
Quality of life |
Supervivencia global
Tasa de respuesta de acuerdo a RECIST 1.1
Acontecimientos adversos de acuerdo a NCI CTC versión 4.0
Calidad de vida |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation with CTscan/ MRI will take place every 2 months
Adverse events will be evaluated every 2 weeks
Quality of life will be evaluated every 2 months |
La evaluación con CTscan/ MRI se realizará cada 2 meses
Los eventos adversos se evaluarán cada 2 semanas
La calidad de vida se evaluará cada 2 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| liosomal irinotecan and 5-fluorouracil |
|
| 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 | 3 |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
| 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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