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    Summary
    EudraCT Number:2008-006182-88
    Sponsor's Protocol Code Number:CRAD001CDE16
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-07-17
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2008-006182-88
    A.3Full title of the trial
    RAMSETE: A single arm, multicenter, single-stage phase II trial of RAD001 in Advanced and Metastatic Silent neuro-Endocrine Tumours in Europe
    A.3.2Name or abbreviated title of the trial where available
    RAMSETE
    A.4.1Sponsor's protocol code numberCRAD001CDE16
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberND
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNOVARTIS FARMA
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/07/449
    D.3 Description of the IMP
    D.3.1Product nameeverolimus
    D.3.2Product code RAD001
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNeverolimus
    D.3.9.1CAS number 159351-69-6
    D.3.9.2Current sponsor codeRAD001
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    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. The multicenters, international trial will enroll maximum 60 patients in 12 months.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 12.0
    E.1.2Level LLT
    E.1.2Classification code 10052399
    E.1.2Term Neuroendocrine tumour
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of RAD001 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
    E.2.2Secondary objectives of the trial
    - 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 RAD001
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Adult male or female patients &amp;#8805; 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: previous &amp;#8804; 1 CT regimen for advanced disease; previous &amp;#8804; 1 RT regimen; previous &amp;#8804; 1 Biotherapy (e.g. IFN etc); previous &amp;#8804; 1 VEGFi therapy (e.g. bevacizumab, sunitinib etc); - Measurable disease as defined by RECIST using instrumental assessment (CT or MRI) - Adequate bone marrow function as shown by: ANC &amp;#8805; 1.5 x 109/L, Platelets &amp;#8805; 100 x 109/L, Hb >9 g/dL - Adequate liver function as shown by: Serum bilirubin &amp;#8804; 1.5 x ULN, INR < 1.3 (or < 3 on anticoagulants), ALT and AST &amp;#8804; 2.5x ULN (&amp;#8804; 5x ULN in patients with liver metastases) - Adequate renal function: serum creatinine &amp;#8804; 2.0 x ULN - Fasting serum cholesterol &amp;#8804;200 mg/dL OR &amp;#8804;5 mmol/L AND fasting triglycerides &amp;#8804;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 &amp;#8805; 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
    E.4Principal exclusion criteria
    - Paients 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 &amp;#8805;4 stools per day and/or flushes). - Ptients with Islet Cell carcinomas or pancreatic NET - Patients who receive currently following therapies have to undergo washout period prior to study entry: Citoxic CT: 4 weeks; Bitherapy: 4 weeks; Biotherapy short acting: 48 hours; Radiotherapy: 4 weeks. - 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 &amp;#8805; 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 (unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction &amp;#8804; 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air, uncontrolled diabetes as defined by fasting serum glucose >1.5x ULN, any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study, nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment, such as severe hypertension that is not controlled with medical management and thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication, liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis, life-threatening autoimmune and ischemic disorders) - Patients who have a history of another primary malignancy and off treatment for &amp;#8804;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.
    E.5 End points
    E.5.1Primary end point(s)
    - Objective Response Rate (CR + PR) - Biochemical response (CgA) - Disease control rate (CR + PR + SD) - Progression-free survival - Overall survival
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other 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.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial 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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2009-09-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-07-15
    P. End of Trial
    P.End of Trial StatusCompleted
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