| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with resected head of pancreas adenocarcinoma |
| Los pacientes con adenocarcinoma de cabeza de páncreas resecado |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with resected head of pancreas adenocarcinoma |
| Los pacientes con adenocarcinoma de cabeza de páncreas resecado |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10052747 |
| E.1.2 | Term | Adenocarcinoma pancreas |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
- Determine whether the addition of erlotinib to gemcitabine adjuvant chemotherapy improves survival as compared to gemcitabine alone following R0 or R1 resection of head of pancreas adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process).
- Determine whether the use of concurrent fluoropyrimidine and radiotherapy following
adjuvant gemcitabine based chemotherapy further enhances survival for such patients who are
without evidence of progressive disease after 5 cycles of gemcitabine based chemotherapy |
- Determinar si la adición de erlotinib a gemcitabina quimioterapia adyuvante mejora la supervivencia en comparación con gemcitabina sola después de una resección R0 o R1 de cabeza de páncreas adenocarcinoma (incluido el adenocarcinoma de la cabeza, el cuello y el proceso unciforme).
- Determinar si el uso de fluoropirimidina concurrente y radioterapia después de
la quimioterapia adyuvante basada en gemcitabina mejora aún más la supervivencia de estos pacientes que son
sin evidencia de enfermedad progresiva después de 5 ciclos de quimioterapia basada en gemcitabina |
|
| E.2.2 | Secondary objectives of the trial |
- Value DFS for all patients and for patients with DFS after 5 cycles of adjuvant chemo.
- Value DFS of standard adjuvant gemcitabine chemo with & without erlotinib for patients with resected head of pancreas adenocarcinoma.
- Value DFS & OS by wild-type & mutant K-Ras status.
- Value AEs
- Value AEs for patients who are disease free after adjuvant chemo.
- Value preoperative cross-sectional imaging of the pancreas primary head adenocarcinoma to determine the frequency with which objective criteria of resectability are present.
- Predictive roles of K-Ras mutations and EMT phenotype.
- Frequency of EGFR activated pathway and its influence on the patients outcome. Association of developmental molecular markers & therapy outcome. Phenotype and genotype of tumors in patients with recurrence after resection.
- Does low baseline fatigue measured by the FACIT-Fatigue, predict survival. Correlations between baseline fatigue, measured by PROMIS, and survival. |
| - DFS de valor para todos los pacientes y en los pacientes con SLE a los 5 ciclos de quimio adyuvante/DFS valor de la quimio adyuvante estándar con gemcitabina con y sin erlotinib en pacientes con adenocarcinoma de cabeza de páncreas resecado/Valor de DFS y OS de tipo salvaje y mutante K-Ras estado/Valor de EA para los pacientes que están libres de la enfermedad después de la quimio. adyuvante/El valor preoperatorio imágenes transversales del adenocarcinoma de páncreas cabeza primaria para determinar la frecuencia con que los criterios objetivos de la resecabilidad están presentes/Funciones de predicción de mutaciones K-ras y el fenotipo EMT/Frecuencia de EGFR vía activada y su influencia en la evolución de los pacientes. Asociación de marcadores moleculares en el desarrollo y evolución de la terapia. Fenotipo y genotipo de tumores en pacientes con recidiva después de la resección/¿La fatiga basal baja medida por el FACIT-Fatiga, predecir la supervivencia. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Histologic proof of primary head of pancreas invasive adenocarcinoma managed with a potentially curative resection (i.e., removal of all gross tumor) involving a classic pancreaticoduodenectomy (Whipple) or a pylorus preserving pancreaticoduodenectomy. Patients with invasive adenocarcinoma that also contains a component of intraductal papillary mucinous neoplasm (IPMN) are eligible
The operating surgeon must document in the operative note that a complete gross excision of the primary tumor was achieved. The pathology report must include documentation of the margin status and the size of the tumor. The pathology report nmust also include the status of the three major margins?bile duct, pancreatic parenchyma, and retroperitoneal (uncinate).
2. Interval between definitive tumor-related surgery and 1st step registration between 21-56 days.
3 Patients will be staged according to the 6th edition AJCC staging system with pathologic stage T1-3, N0-1, M-0 being eligible.
4. Age ? 18.
5 Zubrod performance status 0 or 1.
6 Complete history and physical examination including weight and Zubrod status within 31 days of study entry.
7. Before starting therapy the patient should be able to maintain adequate oral nutrition of ? 1500 calories estimated caloric intake per day and be free of significant nausea and vomiting.
8. CBC/differential obtained within 21 days of registration on study, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ? 1,500 cells/mm3
- Platelets ? 100,000 cells/mm3
- Hemoglobin ? 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ? 8.0 g/dl is acceptable.)
9 Post resection serum CA19-9 ? 180 units/mL within 21 days of registration on study.
10 Patients must have:
- Serum total bilirubin ? twice the institutional upper limit of normal within 21 days of registration on study.
- Creatinine levels ? twice the institutional upper limit of normal within 21 days of registration on study.
- SGOT must be ? 2.5 x the institutional upper limit of normal within 21 days of registration on study.
11 Negative serum pregnancy test for women of childbearing potential within 14 days of study registration.
12 Abdominal/pelvic CT scan with contrast and chest CT/x-ray (CT of chest preferred) within 31 days of registration on study. Patients allergic to IV contrast can have MRI of the abdomen/pelvis instead.
13 Signed study-specific informed consent
14 Consultation, agreement, and documentation in the patient?s chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol.
15 Women of childbearing potential and male participants must practice adequate contraception.
16 Patients with active HIV infection are eligible if their CD4 count is > 499/cu mm and their viral load is < 50 copies/ml; use of HAART is allowed. |
- Prueba histológica de adenocarcinoma primario invasivo de cabeza de páncreas tratado con una resección potencialmente curativa (esto es, extirpación de todo el tumor) mediante una pancreatoduodenectomía clásica (Whipple) o una pancreatoduodenectomía conservadora del píloro.
- Intervalo de entre 21 a 56 días entre la cirugía definitiva relacionada con el tumor y la primera aleatorización.
- Escisión total del tumor primario (R0 o R1) documentada por el cirujano.
- Etapa patológica T1-3, N0-1, M-0 (6.ª edición del sistema de clasificación por etapas del AJCC)
- Estado funcional de Zubrod/OMS/ECOG de 0 o 1.
- El paciente puede recibir radioterapia según este protocolo de acuerdo a lo indicado por el oncólogo radioterapeuta. |
|
| E.4 | Principal exclusion criteria |
1.Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas.
2 Patients managed with a total pancreatectomy, a distal pancreatectomy, or central pancreatectomy.
3 Prior systemic chemotherapy for pancreas cancer; note that prior chemotherapy for a different cancer is allowable.
4 Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
5 Previous history of invasive malignancy (except non-melanoma skin cancer) unless the patient as been disease free for at least 2 years prior to study entry (Patients with a previous history of carcinoma in situ are eligible.
6 Severe, active co-morbidity, defined as follows:
-Unstable angina and/or congestive heart failure requiring hospitalization within the last 6
months
-Transmural myocardial infarction within the 3 months of study registration
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
7 Pregnant or lactating women
8 Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
9 If surgical margin status cannot be determined after consultation with the operating surgeon and the institutional pathologist, the patient will be ineligible. |
1.Patients con no adenocarcinomas, carcinomas de células de los islotes, adenoescamosos (neuroendocrino), los tumores, cistoadenomas, cistadenocarcinomas, los tumores carcinoides, carcinomas duodenales, el conducto biliar distal, y los carcinomas ampulares.
2 Los pacientes manejados con una pancreatectomía total, una pancreatectomía distal, o una pancreatectomía central.
3 Antes de la quimioterapia sistémica para el cáncer de páncreas, tenga en cuenta que antes de la quimioterapia para un cáncer distinto es permisible.
4 radioterapia previa a la región del estudio de cáncer que dé lugar a la superposición de los campos de la terapia de radiación
5 El antecedente de malignidad invasiva (excepto cáncer de piel no melanoma) a menos que el paciente como la enfermedad de estado libre durante al menos 2 años antes del ingreso al estudio (pacientes con una historia previa de carcinoma in situ es elegible.
6 activa, grave co-morbilidad, que se define de la siguiente manera:
-Angina inestable y / o insuficiencia cardíaca congestiva que requieren hospitalización en los últimos 6
meses
-Infarto de miocardio transmural dentro de los 3 meses de inscripción estudio
- La infección aguda por bacterias u hongos que requiere antibióticos por vía intravenosa en el momento de la inscripción
- Obstructiva Crónica exacerbación enfermedad pulmonar u otras enfermedades respiratorias que requieran hospitalización o tratamiento en estudio excluye al momento de la inscripción
7 Las mujeres embarazadas o en período de lactancia
8 Las mujeres en edad fértil y los hombres que tienen relaciones sexuales y no está dispuesto / capaz de utilizar formas médicamente aceptables de anticoncepción, esta exclusión es necesaria porque el tratamiento que participan en este estudio pueden ser significativamente teratogénico.
9 Si el estado del margen quirúrgico no se puede determinar, previa consulta con el cirujano y el patólogo institucional, el paciente podrá ser subvencionada. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1 For the erlotinib question (first randomization): Overall survival (OS) (failure: death due to
any cause)
2 For the chemoradiation question (second randomization): Overall survival (OS) (failure:
death due to any cause) |
1 Para la pregunta erlotinib (primera aleatorización): La supervivencia global (SG) (fracaso: muerte por cualquier causa)
2 Para la pregunta quimiorradiación (segunda asignación aleatoria): La supervivencia global (SG) (fracaso: muerte por cualquier causa) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 3 years after last patient last treatment
2. 2.5 years after last patient second randomization |
1. 3 años después del último tratamiento con último paciente
2. 2,5 años después del último segunda aleatorización paciente |
|
| E.5.2 | Secondary end point(s) |
For both the erlotinib question (first randomization) and the chemoradiation question (second
randomization) unless otherwise noted
1 Disease-free survival (failure: local or regional disease progression, distant metastases,
second primary, or death due to any cause)
2 Adverse events
3 Pre-op imaging to determine frequency of objective criteria of resectability
4 Quality of Life: fatigue as measured by the FACIT-F (primary) and the PROMIS derived
short form (exploratory)
5 Laboratory correlative studies related to K-Ras (first randomization only) |
Por tanto la pregunta erlotinib (primera aleatorización) y la cuestión quimiorradiación (segunda asignación al azar) a menos que se indique lo contrario
1. Supervivencia libre de enfermedad (insuficiencia: progresión de la enfermedad local o regional, metástasis a distancia,
segundo primario o muerte por cualquier causa)
2. Los eventos adversos
3. Pre-op de imágenes para determinar la frecuencia de los criterios objetivos de la resecabilidad
4. Calidad de vida: la fatiga medida por el FACIT-F (primario) y los derivados PROMIS
forma corta (exploratorio)
5. Los estudios de laboratorio correlativos relacionados con K-Ras (asignación al azar sólo la primera) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 1. 1-5: 3 years after last patient last treatment |
| 1. 1-5: 3 años después del último tratamiento del último paciente |
|
| 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 | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
| standard clinical practice |
|
| 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
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 |
|
| 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
|
End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 8 |
| 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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