A single arm, multicenter, single-stage phase II trial of RAD001 in Advanced and Metastatic Silent neuro-Endocrine Tumours in Europe - RAMSETE

• Conditions: 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: 9.1Level: LLTClassification code 10052399Term: Neuroendocrine tumour

• Registration Number: EUCTR2008-006182-88-NL
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-11
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 69

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.
• Measurable 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 < 1.3 (or < 3 on anticoagulants)
• ALT and AST = 2.5x ULN (= 5x ULN in patients with liver metastases)
• Adequate renal function: serum creatinine = 2.0 x ULN
• Fasting serum cholesterol =200 mg/dL OR =5 mmol/L AND fasting triglycerides =200mg/dL. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• ECOG performance status of 0-2
• Life expectancy = 6 months
• Women of childbearing potential must have had a negative urine pregnancy test within one week prior to the administration of the study treatment start.
• Patients who give a written informed consent obtained according to local guidelines
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified