E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal cell carcinomas arise from the proximal tubal epithelium. Alternatively known as clear-cell cancer or renal adenocarcinoma, RCC is characterized by a distinct clear or granular cell appearance visible by light microscopy. The most common molecular abnormality in clear cell RCC is loss of Von Hippel-Lindau (VHL), which is found in about 50-70% of sporadic cases. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare progression-free survival (PFS) in patients who receive RAD001 plus BSC versus patients who receive Matching Placebo plus BSC. |
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E.2.2 | Secondary objectives of the trial |
• To compare the overall survival for patients who received RAD001 plus BSC versus Matching Placebo plus BSC • To compare the objective response rate and duration in patients who receive RAD001 plus BSC versus Matching Placebo plus BSC • To describe the safety profile of RAD001 when compared to Placebo • To assess disease related symptoms and overall QoL in patients treated with RAD001 plus BSC and to compare these patients reported outcomes to the Matching Placebo plus BSC treatment group. • To describe the pharmacokinetics of RAD001 in patients with renal cell cancer. • To explore the relationships between RAD001 blood levels and efficacy/safety endpoints. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years old • Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cancer is acceptable). • Patients must have progression on or within 6 months of stopping treatment with a VEGF receptor tyrosine kinase inhibitor (sunitinib and/or sorafenib). Patients may have received one or both agents. • Prior therapy with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted. • Prior vaccine therapy in the adjuvant setting is permitted. • Patients with at least one measurable lesion at baseline as per the RECIST criteria, either on physical exam or as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI). • Patients with a Karnofsky Performance Status ≥ 70%. • 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: serum bilirubin: ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases: AST and ALT ≤ 5x ULN. • Adequate renal function: serum creatinine ≤ 1.5 x ULN. • Patients with a life expectancy ≥ 6 months. • Women of childbearing potential must have had a negative serum or urine pre gnancy test 48 hours prior to the administration of the first study treatment. • Patients who give a written informed consent obtained according to local guidelines |
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E.4 | Principal exclusion criteria |
• Patients currently receiving chemotherapy, immunotherapy, or radio-therapy or who have received these ≤4 weeks prior to Visit 1. • Patients who have previously received mTOR inhibitors. • Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent • Patients with a known history of HIV seropositivity • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin) • Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients. •Patients with untreated CNS metastases or who are neurologically unstable despite treatment of the CNS metastases. (Patients with treated CNS metastases, who are neurologically stable off of corticosteroids, are eligible to enter study). • Patients who have any severe and/or uncontrolled medical conditions such as: • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to randomization, serious uncontrolled cardiac arrhythmia, • uncontrolled diabetes as defined by fasting serum glucose >1.5X ULN. • active or uncontrolled severe infection. • cirrhosis, chronic active hepatitis or chronic persistent hepatitis • severely impaired lung function • Patients who have a history of another primary malignancy ≤ 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix • 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. • Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to randomization (Visit 2). • Patients unwilling to or unable to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
progression-free survival |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |