E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007275 |
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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 whether treatment with RAD001 10 mg/d plus Sandostatin LAR prolongs the progression free survival (PFS) compared to treatment with Sandostatin LAR alone in patients with advanced carcinoid tumor |
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E.2.2 | Secondary objectives of the trial |
To evaluate the anti-tumor effect of RAD001 on other tumor endpoints (best overall response rate ヨComplete Response (CR) and Partial Response (PR), response duration) ユ To compare overall survival (OS) between the study arms ユ To compare changes from baseline in 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) ユ To determine the safety and tolerability of the combination of RAD001 (10 mg/d) plus Sandostatin LAR ユ To characterize the pharmacokinetics of RAD001 and Sandostatin LAR administered in combination in carcinoid indications Exploratory Objectives: ユ To determine the effects of RAD001 on plasma angiogenic molecules such as VEGF and basic FGF ユ To determine the effects of RAD001 on serum lactate dehydrogenase (LDH) isozymes ユ To characterize pre-treatment tumor samples by immunohistochemical and genetic analyses indicating activation of the mTOR pathway ユ pls see protocol |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Advanced (unresectable or metastatic) biopsy-proven carcinoid tumor Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma 2. Patients must have radiological documentation of progression of disease within 12 months prior to randomization. Progression of disease is demonstrated if there is an unequivocal increase in size of tumors assessed by radiological studies. 3. Measurable disease per RECIST determined by Triphasic Computer Tomography (CT) scan or MRI 4. Adequate bone marrow function as shown by: ANC >= 1.5 x 109/L, Platelets >= 100 x 109/L, Hb >9 g/dL 5. Adequate liver function as shown by: ユ serum bilirubin <= 1.5 x ULN ユ INR < 1.3 x ULN ユ ALT and AST <= 2.5 x ULN (<= 5 x ULN in patients with liver metastases) 6. Adequate renal function: serum creatinine <= 1.5 x ULN 7. Fasting serum cholesterol <= 300 mg/dL OR <= 7.75 mmol/L AND fasting triglycerides <= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. 8. Performance Status 0-2 on the WHO scale 9. Adult male or female patients >18 years of age 10. Women of childbearing potential must have had a negative pregnancy test 11.Signed informed consent and willingness and ability to comply |
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E.4 | Principal exclusion criteria |
Patients with poorly differentiated neuroendocrine carcinoma, highgrade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, goblet cell carcinoid and small cell carcinoma are not eligible . Cytotoxic chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to randomization . Received treatment with Sandostatin LAR Depot or any other longacting somatostatin analog within 2 weeks prior to randomization . 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 randomization . Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus) . Known intolerance or hypersensitivity to octreotide, Sandostatin LAR, RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) . Uncontrolled diabetes mellitus defined by fasting glucose >1.5 X ULN . Patients who have any severe and/or uncontrolled medical condition . Patients receiving chronic treatment with immunosuppressives . Patients with a known history of HIV seropositivity . Patients with bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin) . Patients who have a history of another primary malignancy <= 3 y, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix . Female patients who are pregnant or nursing (lactating), 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PFS evaluated per RECIST and will be assessed by an independent central radiology review. Secondary endpoints will include best overall response rate (CR and PR) and response duration (CR and PR). |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |