RAMSETE: RAD001 in Advanced and Metastatic Silent Neuro-endocrine Tumors in Europe

A Single Arm, Multicenter Single Stage Phase II Trial of RAD001 as Monotherapy in the Treatment of Metastatic Non Syndromic Neuro-endocrine Tumors

To evaluate the preliminary efficacy and safety of RAD001 as monotherapy for first-line treatment of patients with metastatic papillary carcinoma of the kidney.

Inclusion criteria:

1. ≥ 18 years old
2. Patients with advanced (unresectable or metastatic) biopsy proven non-syndromic neuro-endocrine carcinoma, low or intermediate grade
3. Radiological documentation of disease progression within 12 months prior to study entry. If patients received anti-tumor therapy during the past 12 months, they must have radiological documentation of progressive disease (PD) while on or after receiving the therapy
4. Patients may have received previous treatments (chemotherapy, biotherapy, peptide-receptor radionuclide therapy); an overall maximum of 3 systemic treatment is allowed
5. Patients with at least one measurable lesion
6. Patients with an ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2
7. Adequate bone marrow function
8. Adequate liver function
9. Adequate renal function
10. Adequate lipid profile

Exclusion criteria:

1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
2. Patients with carcinoid with hormone related symptoms (diarrhea ≥ 4 stools per day and/or flushes)
3. Patients with Islet cell carcinomas or pancreatic NET
4. Patients who received prior therapy with Vascular Endothelial Growth Factor (VEGF) pathway inhibitor within 4 weeks prior to study entry
5. Patients who entered peptide receptor radionuclide therapy (PRRT) within 3 months prior to study entry
6. Patients who received CT, biotherapy or radiotherapy within 4 weeks prior to study entry
7. Patients who have previously received systemic (mammalian target of rapamycin) mTOR inhibitors
8. Patients with a known hypersensitivity to everolimus or other rapamycins or to its excipients
9. Patients with uncontrolled central nervous system (CNS) metastases
10. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
11. Patients with a known history of HIV seropositivity
12. Patients with autoimmune hepatitis
13. Patients with an active, bleeding diathesis
14. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
15. Patients who have a history of another primary malignancy and off treatment ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix
16. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods
17. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start
18. Patients unwilling to or unable to comply with the protocol