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 | 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 assess the probability that Progression Free Survival during or after first-line (PFS-1L) of treatment in patients who receive RAD001 is non-inferior to the PFS during or after first-line of treatment in patients who receive sunitinib as treatment for metastatic renal cell carcinoma.
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E.2.2 | Secondary objectives of the trial |
• To compare the time from randomization to Progression Free Survival Combining 1st and 2nd line (PFS-C) after second-line of treatment in patients who receive RAD001 followed by sunitinib with PFS-C in patients who receive sunitinib followed by RAD001 as treatment for metastatic renal cell carcinoma. • To compare the safety profile of RAD001 versus sunitinib within the 2 lines strategies. • To assess disease related symptoms and overall quality of life (QoL) in patients treated with RAD001 followed by sunitinib to compare these patients reported outcomes to the sunitinib followed by RAD001 group • To compare the overall survival of patients who receive RAD001 followed by sunitinib versus patients who receive sunitinib followed by RAD001. • To assess the objective response rate and duration of response in patients who receive RAD001 versus patients who receive sunitinib during first-line of treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years old. 2. Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell (or with a component of clear cell) or patients with non-clear cell renal carcinoma. 3. Patients with nephrectomy (partial or total) or without nephrectomy. 4. Patients with at least one measurable lesion at baseline as per the RECIST criteria. If skin lesions are reported as target lesions, they should be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion(s) to be determined from the photograph. 5. Patients with a Karnofsky Performance Status ≥70%. 6. Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL. 7. 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. 8. Adequate renal function: serum creatinine ≤ 2.0 x ULN. 9. Left ventricular ejection fraction (LVEF) lower limit of institutional normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan. The same modality used at baseline should be applied for subsequent evaluations. 10. Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study medication. 11. Patients who give a written informed consent obtained according to local guidelines.
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E.4 | Principal exclusion criteria |
1. Patients within 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry. 2. Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start). 3. Patients in anticipation of the need for major surgical procedure during the course of the study. 4. Patients with a serious non-healing wound, ulcer, or bone fracture. 5. Patients with a history of seizure(s) not controlled with standard medical therapy. 6. Patients who have received prior systemic treatment for their metastatic RCC. 7. Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus) or VEGF inhibitors. 8. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients. 9. Patients with a known hypersensitivity to sunitinib or its excipients. 10. History or clinical evidence of central nervous system (CNS) metastases. 11. Clinically significant gastrointestinal abnormalities. 12. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg]. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. 13. Patients receiving chronic systemic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable. 14. Patients with a known history of HIV seropositivity. 15. Patients with active bleeding. 16. Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study. 17. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) ≤ 6 months before start of study treatment. 18. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. 19. 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 the uterine cervix or breast, and localized cancer of the bladder (T1) and prostate (T1 - T2). 20. 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. 21. Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start. 22. Patients unwilling or unable to comply with the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoints: Progression-free survival (PFS-1L) defined as the time interval between randomization and first documented disease progression or death due to any cause reported during or after first-line treatment.
Secondary efficacy endpoints: • Progression-free survival combine (PFS-C), a composite endpoint defined as the time interval between randomization and second documented disease progression reported during or after second-line or death due to any cause. • Patient reported outcomes (disease-related symptoms and overall quality of life [QoL] using the FKSI-DRS and EORTC QLQ-C30) • Overall survival (OS) defined as the time interval between randomization and death due to any cause • Objective response rate after first-line of treatment
Safety endpoints • Incidence of adverse events leading to study drug discontinuation during first-line. • Time to adverse events with suspected relationship or leading to study drug discontinuation or death due to toxicity during first-line. • Incidence of adverse events, serious adverse events, incidence of laboratory abnormalities (hematology, blood chemistry and urinalysis).
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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 | Yes |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |