| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Potentially resectable pancreatic cancer |
| Carcinoma de páncreas potencialmente resecable |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pancreatic cancer which can be surgically resected. |
| Cancer de páncreas que puede ser operado |
|
| 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 | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033608 |
| E.1.2 | Term | Pancreatic cancer resectable |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 variation of the elastographic index between patients treated with Gemcitabine plus nab-paclitaxel and patients treated with FOLFIRINOX |
| Comprobar la variación en el índice de elastografía entre los pacientes tratados con gemcitabina mas nabpaclitaxel y los tratados con FOLFIRINOX |
|
| E.2.2 | Secondary objectives of the trial |
- To compare Cancer Associated Fibroblasts (CAF) density in the tumor samples between both arms
- To assess tumor response by RECIST criteria in both arms
- To determine the surgery rates in both arms and rates of R0 resections (R0 is defined as complete resection with no tumor within 1 mm of resection margins) in both arms.
- Histological response (according to Ryan criteria) in both arms.
- Progression-free survival in both arms.
- Overall survival in both treatment groups
- To measure tumor vascularization changes by MisoPet before and after treatment with FOLFIRINOX and with Gemcitabine plus nab-paclitaxel, and their correlation with vascularization of the surgical sample in both arms.
- Determine CA19.9 decrease in patients treated with FOLFIRINOX and patients treated with Gemcitabine plus nab-paclitaxel at the end of the neoadyuvant treatment.
- Assessment of CA19.9 early decrease in both arms |
- Comparar la densidad de CAF (fibroblastos activados) entre ambos brazos
- Valoración de respuesta tumoral mediante criterios RECIST en uno y otro brazo.
- Tasa de cirugías en ambos brazos y tasa de cirugía R0 (borde de resección a más de 1mm) en ambos brazos.
- Valoración de respuesta histológica (según adaptación de criterios de Ryan) en uno y otro brazo.
- Supervivencia libre de progresión en uno y otro brazo
- Supervivencia Global en cada uno de los brazos
- Medición de cambios de la vascularización tumoral por MisoPET antes y después del tratamiento en ambos brazos y su correlación con la vascularización en la pieza quirúrgica en ambos brazos.
- Valoración del descenso de CA19.9 en pacientes tratados con FOLFIRINOX y con GemNabPTX al finalizar el tratamiento neoadyuvante.
- Valoración del descenso precoz de CA19.9 en pacientes tratados con FOLFIRINOX y con nabpaclitaxel (descenso precoz se considera descenso mayor de 20% en el primer mes de tratamiento) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1- Patients with cytological or anathomopathological diagnosis of pancreatic carcinoma
2- The pancreatic tumor is resectable or borderline
3- Older than 18 years
4- ECOG performance status 0-1
5- Adequate hematologic function:
a. Neutrophils > 1.500
b. Hemoglobin > 9
c. Platelets > 100.000
6- Adequate liver and kidney function:
a. Bilirubin <= 1,5 ULN
b. AST <= 3 ULN
c. ALT ? 3 ULN
d. Creatinine clearance >= 40ml/min
7- Signed informed consent |
1.- Pacientes con diagnóstico o citológico anatomopatológico de carcinoma de páncreas
2.- El tumor de páncreas es resecable o borderline.
3.- Edad mayor de 18 años
4.- Buen estado funcional medido como ECOG 0-1
5.- Adecuado perfil de hemograma:
- Neutrófilos >1500
- Hemoglobina > 9
- Plaquetas >100.000
6.- Adecuado perfil bioquímico
- Bilirubina <= 1,5 ULN
- AST <= 3 ULN
- ALT <= 3 ULN
- Aclaramiento de Creatinina >=40ml/min
7.- Firma de Consentimiento Informado |
|
| E.4 | Principal exclusion criteria |
1.- Patients unable to complete the study procedures for geographical, psychiatric or social reasons.
2.- Patients with some physical or psychical condition which contraindicates the study treatment
3.- Patients with active infection or another significant or autoimmune disease.
4.- ECOG performance status >= 2.
5.- Chronic hepatic disease (cirrhosis, chronic hepatitis)
6.- Another solid or hematologic concurrent tumor or previous tumors for the last 5 years. (except for basal cell carcinoma and skin epidermoid no relapsed tumors)
7.- Pregnancy or breastfeeding period. Women of child-bearing potential and men have to use contraceptive methods or be surgically sterilized.
8.- Patients who are taking oral anticoagulants and it cannot be replaced for subcutaneous low molecular weight heparin.
9.- Distant pancreatic cancer metastasis.
10.- Patients who have been previously treated for pancreatic carcinoma with radiotherapy, chemotherapy or surgical treatment different from biliary derivation or biopsy.
11.- Impossibility or contraindication to complete any study procedure (Eco-endoscopy, NMR, MisoPET)
12.- Prior history of neuropathy or polyneuropathy |
1. Pacientes que no puedan completar los procedimientos del estudio por motivos geográficos, psiquiátricos o razones sociales.
2. Pacientes con cualquier condición física o psíquica que, a criterio del investigador, contraindique el tratamiento dentro de estudio.
3. Infección activa u otra enfermedad grave o trastorno autoinmune.
4. Estado funcional no óptimo medido como ECOG mayor o igual a 2
5. Enfermedad crónica hepática conocida (cirrosis, hepatitis crónica).
6. Otros tumores sólidos o hematológicos concurrentes o historia de tumores previos en los últimos 5 años (a excepción de tumores basocelulares o epidermoides de piel no recaídos).
7. Embarazo o lactancia. Las mujeres que estén en edad fértil deben aceptar usar un método anticonceptivo si no son quirúrgicamente estériles.
8. Pacientes que estén recibiendo anticoagulación oral y no se pueda modificar por heparina de bajo peso subcutánea.
9. Metástasis a distancia de adenocarcinoma de páncreas
10. Haber recibido tratamiento previo para carcinoma de páncreas ya sea radioterapia, quimioterapia o tratamiento quirúrgico diferente a derivación biliar o intervención para obtener muestra.
11.- Imposibilidad o contraindicación para realizar cualquier procedimiento del estudio (ECOendoscopia, RMN, MisoPET)
12.- Antecedente de neuropatía o polineuropatía previa |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The means of the difference in elastographic values before and after treatment in both arms will be compared |
| Se comparará la media de diferencia del valor de elastografía antes y después del tratamiento en cada uno de los brazos |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Before and after both arms treatment |
| Antes y después del tratamiento |
|
| E.5.2 | Secondary end point(s) |
- PET-TAC.- 18FDG-PET will be used for measure SUV max (Standard Uptake Value max) for pancreatic lesion. EORTC criteria will be following in order to assess PET response.
- CA19.9 response
- Thorax-abdomen-pelvis TAC with iv contrast. RECIST 1.1 criteria will be followed. For response evaluation: ((Post-basal value ? basal value)/basal value) x 100. The following definitions will be used for assess the response. Complete response (CR) if the target lesion disappears; Partial response (PT) if the target lesion decreases at least 30%; Disease progression (DP) if the target lesion increases 20% or more. Stable disease (SD) if the lesion cannot be included in DP or PT categories. If the target lesion cannot be measure correctly it will be no gradable (NG).
- MISO-PET to assess the tumor vascularization.
- Assessment of tumor sample: 1.- Resection margins which could be R0, R1 or R2. 2.- Regression degree of the histological response by the following scale: (0) No tumor; (1) tumor cells, isolated tumor nests; (2) frequent tumor nests; (3) minimal response; (4) no response. |
- PET-TAC.- Se realizará 18FDG-PET-TAC para medir el SUV max (Standard Uptake Value max) de la lesión pancreática. Se seguirán criterios de la EORTC para la valoración de la respuesta por PET.
- Respuesta de CA19.9
- TAC de torax-abdomen-pelvis e incluirá contraste intravenoso. Se seguirán criterios RECIST 1.1. Para evaluar la respuesta : ((Valor posbasal ? valor basal)/valor basal) x 100. Respuesta completa (RC) si la lesión desaparece; Respuesta parcial (RP) si la lesión se reduce más de un 30%, Progresión de la enfermedad (PE) si la lesión aumenta al menos el 20%, Enfermedad estable (EE) si no llega a valores de PE ni RP. Si la lesión no se puede medir correctamente será no evaluable (NE).
- MISO-PET para evaluar a vascularización del tumor
- Valoración de la pieza tumoral: 1.- Borde de resección que puede evaluarse como R0, R1, R2. 2.- Grado de regresión de la respuesta histológica usando la siguiente escala: (0) No tumor; (1) Células, nidos tumorales aislados; (2) Nidos tumorales frecuentes; (3) Mínima respuesta; (4) Ausencia de respuesta |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PET-TAC, CA19.9 response, MISO-PET, Thorax-abdomen-pelvis TAC - Before and after treatment
Assessment of tumor simple - After treatment |
PET-TAC, Respuesta de CA19.9, MISO-PET, TAC de tórax-abdomen-pelvis - Antes y después de los dos brazos de tratamiento
Valoración de la pieza tumoral - Después del tratamiento |
|
| 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 | 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 | 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 | 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 21 |
| E.8.9.1 | In the Member State concerned days | |
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