| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with pancreatic ductal adenocarcinoma |
| pazienti affetti da adenocarcinoma del pancreas |
|
| E.1.1.1 | Medical condition in easily understood language |
| pancreatic cancer |
| tumore del pancreas |
|
| 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 | 21.0 |
| 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 |
|
| 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 compare in terms of 1yr-EFS the efficacy of PAXG to that of mFOLFIRINOX.
to compare in terms of 1yr-EFS the efficacy of 4 months pre-operative and 2 months postoperative chemotherapy to that of 6 months of pre-operative chemotherapy |
confrontare in termini di EFS ad 1 anno l'efficacia di PAXG a quella di mFOLFIRINOX.
confrontare in termini EFS ad 1 anno l'efficacia di 4 mesi di chemioterapia preoperatoria e 2 mesi postoperatoria a quella di 6 mesi di chemioterapia preoperatoria |
|
| E.2.2 | Secondary objectives of the trial |
| OS, RECIST response rate, CA19.9 response rate, and complete pathologic response, resectability rate, surgical mortality and morbidity rate, intra- and post-operative metastasis rate, N0 and R0 resections rate, patients reported outcomes, and treatment toxicity |
| valutare l'OS, il tasso di risposta RECIST, il tasso di risposta del CA19.9 e la risposta patologica completa, il tasso di resecabilità, la mortalità chirurgica e il tasso di morbilità, il tasso di metastasi intra e post-operatorio, il tasso di resezioni N0 e R0, il PRO e la tossicità del trattamento. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Cyto/histological diagnosis of pancreatic ductal adenocarcinoma*;
2. Clinical stage I-III disease according to TNM 8th Ed. 2017 [appendix 1];
3. Resectable or borderline resectable disease, as anatomically defined according to NCCN Guidelines Version 1.2020
4. Karnofsky Performance Status > 60% [appendix 3];
5. Age ¿ 18 and = 75 years;
6. Adequate bone marrow function (GB = 3500/mm3, neutrophils =1500/mm3, platelets = 100000/mm3, Hb =10 g/dl);
7. Adequate kidney function (serum creatinine < 1.5 mg/dL);
8. Adequate liver function (ALT and AST < 3 ULN and Serum total bilirubin = 1.5 ULN);
9. No prior treatment (chemotherapy, radiotherapy and/or surgery) for pancreatic cancer;
10. Women must not be on pregnancy or lactation;
11. Patient of child-bearing potential must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for 4 months after the last study treatment intake for women and 6 months for men;
12. Patient information and signed written informed consent. |
1. Diagnosi patologica di adenocarcinoma duttale pancreatico (PDAC)
2. Stadio I-III
3. Tumore resecabile o al limite della resecabilità secondo NCCN Guidelines Versione 1.2020
4. Karnofsky > 60%
5. Età compresa tra 18 e 75 anni
6. Midollo osseo adeguato (GB = 3500/mm3; neutrofili >1500/mm3; piastrine > 100000/mm3; emoglobina > 10 g/dl)
7. Funzione epatica adeguata (ALT e AST < 3 ULN)
8. Bilirubina totale del siero < 1,5 ULN
9. Funzione renale adeguata (creatinina <1 ,5 mg/dL)
10. Nessuna chemioterapia, radioterapia o intervento cirurgico precedente per tumore del pancreas
11. Nessuna gravidanza o allattamento
12. Consenso informato scritto |
|
| E.4 | Principal exclusion criteria |
1. Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and other periampullary malignancies.
2. Prior or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasms without evidence of disease at least from 5 years;
3. Symptomatic duodenal stenosis;
4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
5. Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications
6. Clinical stage IV (including ascites or malignant pleural effusion) disease according to TNM 8th Ed. 2017 [appendix 1];
7. Locally advanced disease according to NCCN Guidelines Version 1.2020 – Pancreatic Adenocarcinoma [appendix 2];
8. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. T
9. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
10. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
11. Any condition that confounds the ability to interpret data from the study
12. Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up;
13. Pre-existing neuropathy, Gilbert's disease or genotype UGT1A1 * 28 / * 28.
14. mutation in DPYD
15. Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine.
16. Concurrent treatment with other experimental drugs;
17. Fructose intolerance |
1. Altri tipi di tumore non-duttale del pancreas, compresi i tumori endocrini o a cellule acinari, i cistoadenocarcinomi e altri tumori periampollari
2. Pregresso o simultaneo tumore in altri siti ad eccezione del carcinoma curato chirurgicamente in-situ della cervice e del carcinoma a cellule basali o squamose della pelle e di altre neoplasie senza evidenza di malattia da almeno 5 anni
3. Stenosi duodenale sintomatica;
4. Infezioni batteriche, virali o fungine attive e incontrollate che richiedono una terapia sistemica;
5. Storia nota di epatite B o C o di HIV o soggetti riceventi terapia immunosoppressiva o mielosopressiva che potrebbero aumentare il rischio di complicazioni da neutropenia;
6. Stadio IV (inclusa ascite o versamento pleurico) in accordo alla classificazione TNM 8th Ed. 2017
7. Tumore localmente avanzato in accordo alle linee guida NCCN Guidelines Version 1.2020
8. Seri fattori di rischio che possono coinvolgere i principali organi o seri disturbi psichiatrici che potrebbero compromettere la salute del paziente o l’integrità dello studio.
9. Qualsiasi condizione medica, anormalità di laboratorio o malattia psichiatrica che a parere del medico potrebbe interferire con lo studio.
10. Qualsiasi condizione, compresa la presenza di anomalie di laboratorio, che pone il soggetto a rischio inaccettabile se dovesse partecipare allo studio
11. Qualsiasi condizione che confonda la capacità di interpretare i dati dello studio
12. Qualsiasi condizione fisiologica, familiare, sociologica o geografica che possa interferire con l'adesione al protocollo o al follow-up
13. Pregressa neuropatia, malattia di Gilbert o genotipo UGT1A1 * 28 / * 28.
14. Mutazioni DPYD
15. Malattia infiammatoria del colon e nel retto o occlusione o sub-occlusione intestinale
16. Trattamento simultaneo con altri farmaci sperimentali
17. Intolleranza al fruttosio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
EFS,
CA19-9 failure
recurrence;
preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. |
EFS,
CA19-9 failure
progressione/ricorrenza,
non resecabilità preoperatoria o intraoperatoria, evidenza intraoperatoria di metastasi o decesso, a seconda di quale si verifichi per primo. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| EFS, defined as the time from randomization to: RECIST progression [At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression]; CA19-9 failure (defined as 2 consecutive increases of serum level =20%, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be. |
| l’EFS, definito come il tempo dalla randomizzazione alla progressione RECIST, CA19-9 failure definito come 2 aumenti consecutivi del livello sierici del marcatore del 20%, dosati ad un intervallo di tempo di 4 settimane, progressione/ricorrenza, non resecabilità preoperatoria o intraoperatoria, evidenza intraoperatoria di metastasi o decesso, a seconda di quale si verifichi per primo. Le resezioni R1 NON saranno considerate come eventi. |
|
| E.5.2 | Secondary end point(s) |
EFS,
CA19-9 failure
recurrence;
preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. |
EFS,
CA19-9 failure
progressione/ricorrenza,
non resecabilità preoperatoria o intraoperatoria, evidenza intraoperatoria di metastasi o decesso, a seconda di quale si verifichi per primo. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| EFS, defined as the time from randomization to: RECIST progression [At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression]; CA19-9 failure (defined as 2 consecutive increases of serum level =20%, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be. |
| l’EFS, definito come il tempo dalla randomizzazione alla progressione RECIST, CA19-9 failure definito come 2 aumenti consecutivi del livello sierici del marcatore del 20%, dosati ad un intervallo di tempo di 4 settimane, progressione/ricorrenza, non resecabilità preoperatoria o intraoperatoria, evidenza intraoperatoria di metastasi o decesso, a seconda di quale si verifichi per primo. Le resezioni R1 NON saranno considerate come eventi. |
|
| 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 | 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 | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Studio di fase II in aperto, multicentrico, randomizzato, comparativo |
| Phase II open label, multicenter, randomized comparative trial. |
|
| 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
| 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 | 22 |
| 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 | Information not present in EudraCT |
| 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 | 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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