| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| pancreatic neuroendocrine tumor (NET) |
| tumori neuroendocrini 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10055007 |
| E.1.2 | Term | Carcinoid tumour of the 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 |
| To determine the objective response rate (ORR) (including complete response and partial response) of RAD001 10 mg po qd monotherapy in patients with advanced (unresectable or metastatic) pancreatic NETs after the failure of cytotoxic chemotherapy (stratum 1). |
| • Valutare la percentuale di risposta obiettiva (completa o parziale) a RAD001 10 mg, somministrato in monoterapia, una volta al giorno per via orale, in pazienti con tumori pancreatici neuroendocrini in stadio avanzato (non operabili o metastatici) dopo insuccesso della chemioterapia citotossica (strato 1). |
|
| E.2.2 | Secondary objectives of the trial |
| -the response duration of RAD001 10 mg po qd monotherapy (stratum 1). •the objective response rate (ORR) and response duration of RAD001 10 mg po qd plus Sandostatin LAR Depot therapy in patients whose tumors have progressed while receiving Sandostatin LAR Depot therapy and after the failure of cytotoxic chemotherapy (stratum 2). - safety and tolerability of RAD001 monotherapy (10 mg/d) in patients with Pancreatic NET (stratum 1). •-safety and tolerability of the combination of RAD001 (10 mg/d) plus Sandostatin LAR Depot in patients with Pancreatic NET (stratum 2). • - progression free survival (PFS) and the overall survival (OS) of patients receiving RAD001 10 mg per day in combination with Sandostatin LAR and of patients receiving RAD001 10 mg per day monotherapy. • To assess the steady state exposure to RAD001 and to estimate the effect of coadministering Sandostatin LAR Depot on RA |
| •Valut la durata della risp a RAD001 10 mg,sommin in monoterapia,1 volta algg per via orale(strato 1).•Valut la % di risp obiettiva e la durata della risp a RAD001 10 mg,sommin una volta algg per via orale,in associazione a Sandostatina LAR Depot,in paz con tumori pancreatici neuroendocrini che hanno presentatoprogr durante la terapia con Sandostatina LAR Depot e dopo insuccesso della chemioterapia citotossica(strato 2).•Valut la sicur.e la toll di RAD001 in monoterap (10 mg/die)in paz con tumori pancreatici neuroendocrini(strato 1).•Valut la sicur.e la toll dell'associazione di RAD001(10 mg/die)e Sandostatina LAR Depot in paz con tumori pancreatici neuroendocrini(strato 2).•Valut la PFS e la sopravvivenza globale(OS)nei paz in terapia con RAD001 10 mg/die in associazione a Sandostatina LAR Depot e nei paz in monoterapia con RAD001 10 mg/die.•Valut l'esposizione a RAD001 allo 'steady state' e l'eff della concomitante sommin di Sandostatina LAR Depot sull'esposizione a RAD001 |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI:
identificazione di indicatori biologici sperimentali
|
|
| E.3 | Principal inclusion criteria |
| Adult male or female patients (>=18 years of age). 2. Advanced (unresectable or metastatic) biopsy-proven pancreatic NET documented as follows: • Radiologic, operative, or pathology reports should document a pancreatic location of tumor at some point in the patient's history; • Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma. Pathology report should state one of the following: carcinoid, islet cell carcinoma, pancreatic endocrine tumor, low-grade or well-differentiated neuroendocrine carcinoma, atypical carcinoid, intermediate-grade or moderately differentiated neuroendocrine carcinoma; • Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma are not eligible. 3. Documented objective progression of disease by RECIST criteria while receiving cytotoxic chemotherapy or documented progression at any time after receiving an adequate course of cytotoxic chemotherapy (i.e., at least 3 consecutive cycles or months of treatment with the same cytotoxic drug or regimen). Previous therapy with alpha interferon or tyrosine kinase inhibitors are allowed but would not be considered to be prior chemotherapy. Objective progression of disease must be documented by RECIST criteria. Any of the following would be sufficient according to RECIST: • a 20% increase in the sum of unidimensionally measured target lesions; • a new lesion; • unequivocal increase in non -measurable disease. |
| 1.Entrambi i sessi ed eta' >= 18 anni. 2.Pazienti con tumore pancreatico neuroendocrino in stadio avanzato (non operabile o metastatico), confermato da biopsia, in base ai seguenti criteri: - La localizzazione pancreatica del tumore deve essere documentata in anamnesi dai referti radiologici o da altri referti medici; - I pazienti devono avere un carcinoma neuroendocrino confermato di grado basso o intermedio. I referti patologici devono riportare: carcinoide, carcinoma a cellule insulari, tumore pancreatico endocrino, carcinoma neuroendocrino a basso grado di differenziazione o ben differenziato, carcinoide atipico, carcinoma neuroendocrino di grado intermedio di differenziazione o moderatamente differenziato. - I pazienti con carcinoma neuroendocrino scarsamente differenziato, carcinoma neuroendocrino ad alto grado di differenziazione, adenocarcinoide, carcinoide a cellule caliciformi e carcinoma a piccole cellule non sono eligibili allo studio. 3.Progressione obiettiva documentata della malattia in base ai criteri RECIST durante chemioterapia citotossica o progressione documentata in qualsiasi momento dopo aver ricevuto un adeguato trattamento con chemioterapia citotossica (tre cicli consecutivi o almeno 3 mesi di trattamento con lo stesso regime chemioterapico). La terapia precedente con interferone-alfa o inibitori della tirosin chinasi e' consentita ma non sara' considerata come precedente chemioterapia. Progressione obiettiva della malattia in base ai criteri RECIST (sara' sufficiente la presenza di uno dei criteri seguenti: aumento del 20% della somma delle lesioni target (misurazione unidimensionale); presenza di una lesione nuova; aumento inequivocabile della malattia non misurabile. |
|
| E.4 | Principal exclusion criteria |
| Anticancer therapy within 3 weeks of enrollment including chemotherapy, hormonal therapy, immunotherapy, surgery or radiotherapy. Investigational agents used solely for imaging purposes are permissible if deemed safe and acceptable by local review authorities. Sandostatin LAR Depot is allowed in stratum 2. 2. Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation of hepatic metastasis within 2 months of enrollment. 3. Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus). 4. Patients with uncontrolled diabetes mellitus as defined by fast blood sugar > 1.5 x ULN. 5. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. 6. Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy. 7. No other prior or concurrent malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years. 8. Known history of immunocompromise, including a positive HIV test. An HIV test will not be required; however, previous medical history will be reviewed. 9. Pregnant or nursing (lactating) women. Unless demonstrated to be post-menopausal (see inclusion criteria), pregnancy should be excluded by serum pregnancy test. 10. Concomitant medications known to inhibit, induce or be a substrate to isoenzyme CYP3A are excluded unless the drugs are medically necessary and no substitutes are available. If there are no acceptable substitutes, special precautions should be taken in these patients. |
| 1.Terapia antitumorale nelle 3 settimane precedenti l'arruolamento, comprendendo la chemioterapia, la terapia ormonale, l'immunoterapia, la chirurgia e la radioterapia. La Sandostatina LAR Depot e' consentita nei pazienti dello strato 2. 2.Embolizzazione dell'arteria epatica nei 6 mesi precedenti (1 mese se sono presenti altre sedi di malattia misurabile) o crioablazione di metastasi epatiche nei 2 mesi precedenti l'arruolamento. 3.Terapia precedente con RAD001 (everolimus) o altre rapamicine (sirolimus, temsirolimus). 4.Diabete mellito non controllato, definito dalla presenza di glicemia a digiuno > 1,5 x ULN. 5.Epatopatie quali cirrosi, epatite cronica attiva o epatite cronica persistente. 6.Infezioni gravi intercorrenti o patologie non maligne non controllate o il cui controllo puo' essere compromesso dalle complicanze della terapia dello studio. 7.Altre patologie maligne precedenti o concomitanti, escludendo adenocarcinoma a cellule squamose della cute o altro carcinoma in situ adeguatamente trattato od ogni altro carcinoma per il quale il paziente e' stato 5 anni libero da progressione. 8.Anamnesi positiva per immunocompromissione, compresa la sieropositivita' HIV. Il test HIV non e' richiesto, tuttavia, sara' necessario eseguire un'anamnesi accurata. 9.Gravidanza e allattamento. Donne potenzialmente fertili che non praticano un metodo contraccettivo efficace. Le donne potenzialmente fertili devono aver eseguito un test di gravidanza sul siero prima del trattamento in studio. Sono ammesse le donne in post-menopausa confermata (vedi criteri di inclusione). 10.Trattamento con farmaci noti inibitori, induttori o substrato degli isoenzimi del sistema CYPA3 a meno che tale trattamento non sia assolutamente necessario e non esistano alternative (in questo caso sara' necessario osservare particolare cautela). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Objective response rate (CR + PR) |
| Percentuale di risposta obiettiva (CR + PR) |
|
| 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 | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 5 |
| 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 | Information not present in EudraCT |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 28 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 28 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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