Patients with histologically confirmed advanced (unresectable or metastatic) non syndromic NET from foregut, midgut and hindgut, with exclusion of pancreatic NET, who have progressed within 12 months prior to study enrollment and with measurable disease at baseline. Patients with poorly differentiated tumours are excluded. MedDRA version: 9.1 Level: LLT Classification code 10052399 Term: Neuroendocrine tumour
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adult male or female patients = 18 years of age • Advanced (unresectable or metastatic) biopsy-proven non syndromic neuro-endocrine carcinoma, low- or intermediate grade • Radiological documentation of disease progression within 12 months prior to study entry. If patients received anti-tumour therapy during the past 12 months, they must have radiological documentation of progression of disease while on or after receiving the therapy. • Patients may have received previous treatment (chemotherapy, biotherapy, peptide-receptor radionuclide therapy ); an overall maximum of 3 systemic treatments is allowed, as follows. • Measurable disease as define: o previous =1 CT line for advanced disease; o previous = RT line; o previous = Biotherapy (e.g. IFN etc); octreotide and/or interferon. In case of previous octreotide and previous interferon, these will be counted as 2 previous systemic treatment lines. o previous = VEGFi treatment line (e.g. bevacizumab, sunitinib etc) Measureable disease as defined by RECIST using instrumental assessment (CT or MRI) • Adequate bone marrow function as shown by: • ANC = 1.5 x 109/L, • Platelets = 100 x 109/L, • Hb >9 g/dL • Adequate liver function as shown by: • Serum bilirubin = 1.5 x ULN • INR =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma are not eligible • Patients with carcinoid with hormone related symptoms (diarrhea =4 stools per day and/or flushes). • Patients with Islet Cell carcinomas or pancreatic NET • Patients who receive currently following therapies have to undergo washout period prior to study entry • The patient should have recovered from the treatment and have a good clinical condition before entering this study. • Patients who received peptide-receptor radionuclide therapy within 3 months prior to study entry • Patients who received VEGFi therapy within 4 weeks prior to study entry. • Patients who received hepatic artery embolisation within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation or radiofrequency ablation of hepatic metastasis within 2 months of study entry • Patients who received prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus) • Patients with a known hypersensitivity to RAD001(everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients • Patients with uncontrolled central nervous system (CNS) metastases. • Patients with an active, bleeding diathesis. • Patients receiving chronic systemic treatment with corticosteroids (dose of = 10 mg/day methylprednisone or equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable. • Patients with a known history of HIV seropositivity. • Patients with autoimmune hepatitis. • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study. • Patients who have a history of another primary malignancy and off treatment for =3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine cervix • Patients that are currently, or in the 4 weeks preceding initiation of study treatment, receiving other investigational agents • Patients unwilling or unable to comply with the requisites of the protocol • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Oral contraceptives are not acceptable. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to randomisation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): • Objective Response Rate (CR + PR) • Biochemical response (CgA) • Disease control rate (CR + PR + SD) • Progression-free survival • Overall survival;Main Objective: To evaluate the efficacy of everolimus as monotherapy in patients with non syndromic neuro-endocrine tumours (NET). Efficacy is defined as the proportion of patients with complete (CR) or partial response (PR) according to RECIST criteria.;Secondary Objective: • To evaluate the disease control rate (CR + PR + SD) • To evaluate the biochemical response rate based on the tumour marker CgA • To evaluate progression-free survival in this patient population • To evaluate overall survival in this patient population • To further characterize the safety profile of everolimus | — |
Countries
Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed