E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with metastatic carcinoma of the kidney who are intolerant of or have progressed despite any available vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
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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 evaluate additional safety of RAD001 in patients with MRCC who are intolerant of or whose disease has progressed despite any available prior VEGF receptor tyrosine kinase inhibitor therapy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the investigators best overall response rate of RAD001 in patients with MRCC who are intolerant of or whose disease has progressed despite any available prior VEGF receptor tyrosine kinase inhibitor therapy. To provide expanded access to RAD001 in patients with MRCC who are intolerant of or whose disease has progressed despite VEGF receptor tyrosine kinase inhibitor therapy, until the product is commercially available [not applicable in the UK and Norway] for MRCC in each participating country or until 15 Jun 2010. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients ≥ 18 years old. Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cell cancer is acceptable). Patients who are intolerant of or have progression on or after stopping treatment with any available VEGF receptor tyrosine kinase inhibitor therapy. Prior vaccine therapy or treatment with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted. Patients with measurable or non-measurable disease by RECIST criteria as determined by the investigator. Patients with history of another distinguishable malignancy [such as non-melanoma skin cancer, low grade lymphoma, chronic lymphocytic leukemia (CLL), or well controlled low grade prostate cancer], which are neither life threatening nor require chemotherapy and/or radiation will be permitted. Patients with history of brain metastasis who are neurologically stable following definitive radiation and/or surgery and do not require corticosteroids will be permitted. Patients with a Karnofsky Performance Status ≥ 70%. Patients with adequate bone marrow function defined as ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hgb >9 g/dL. Patients with adequate liver function defined as serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases who have an AST and ALT ≤ 5x ULN. Patients with adequate renal function defined as serum creatinine ≤ 2 x ULN. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to the first dose of study drug. Patients must give written informed consent according to local guidelines. |
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E.4 | Principal exclusion criteria |
Patients receiving chemotherapy, immunotherapy, radiation therapy or any other investigational agent (including pazopanib) within 4 weeks of the first dose of study drug, or sunitinib and/or sorafenib within 1 week of the first dose of RAD001. Patients who have previously received RAD001 or other mTOR inhibitors. Patients with known hypersensitivity to RAD001 or other rapamycin analogs (sirolimus, temsirolimus), or to its excipients. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of RAD001. Topical or inhaled corticosteroids are permitted. Patients with an active bleeding diathesis. Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g., intra-thoracic, intra-abdominal, or intra-pelvic), open biopsy, or significant traumatic injury, or who have not recovered from the side effects of any of the above. Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. Uncontrolled diabetes (fasting glucose > 2 x ULN). Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not willing to use effective birth control methods. If barrier contraceptives are used, they must be continued throughout the study by both sexes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: Grade 3 and 4 Adverse Events, Serious Adverse Events |
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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 | No |
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | 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.8.4.1 | Number of sites anticipated in Member State concerned | 35 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 119 |
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 | 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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |