E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pacientes con carcinoma renal metastásico de células claras
Patients with metastatic clear cell carcinoma of the kidney |
|
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 |
|
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 treatment effect on progression-free survival (PFS) of RAD001 plus bevacizumab versus patients who receive IFN and bevacizumab based on an estimation of the chance of success of a possible subsequent phase III study. |
|
E.2.2 | Secondary objectives of the trial |
? To estimate the overall survival (OS) treatment effect in patients who receive RAD001 plus bevacizumab versus patients who receive IFN and bevacizumab. ? To estimate the objective response rate and response duration differences in patients who receive RAD001 plus bevacizumab versus patients who receive IFN and bevacizumab. ? To describe the safety profile of RAD001 plus bevacizumab versus IFN and bevacizumab. ? To compare patient reported outcomes on quality of life (QoL) from patients treated with RAD001 plus bevacizumab versus patients treated with IFN and bevacizumab. ? To measure the exposure of RAD001 in patients randomized to the treatment combination of RAD001 and bevacizumab. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ? 18 years old 2. Patients with metastatic renal cell carcinoma and with histological or cytological confirmation of clear cell RCC (pathology report based on the tissue from the original diagnosis of renal cell cancer is acceptable). Any percentage of clear cell histology is acceptable. 3. Patients with at least one measurable lesion at baseline as per the RECIST criteria. If skin lesions are reported as target lesions, they must 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. 4. Patients who had a prior partial or complete nephrectomy. Partial nephrectomy is allowed only if the resection margins were clearly negative. 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. INR and PTT < 1.5. (Anticoagulation is allowed if target INR ? 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of randomization.) 10. Adequate lipid profile: total cholesterol < 300 mg/dL and triglyceride < 200 mg/dL. 11. Women of childbearing potential must have had a negative serum pregnancy test 72 hours prior to the administration of the study treatment start. 12. Patients who give a written informed consent obtained according to local guidelines. |
|
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 28 days 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. Adjuvant immunotherapy (vaccines acceptable, but no cytokines) completed 3 months prior to study treatment start is acceptable. 7. Patients who received prior therapy with VEGF pathway inhibitor (even in the adjuvant setting), such as sunitinib, sorafenib, and bevacizumab. 8. Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus). 9. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients. 10. Patients with evidence of current central nervous system (CNS) metastases or spinal cord compression. 11. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment. 12. Patients with proteinuria at screening as demonstrated by either: ? Urine protein: creatinine (UPC) ratio ? 1.0 at screening. ? Urine dipstick for proteinuria ? 2+ (patients discovered to have ?2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ? 1g of protein in 24 hours to be eligible). 13. Patients with inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy. 14. Patients receiving ongoing or with recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (>75 mg/day). 15. Patients receiving chronic systemic treatment with corticosteroids (dose of ? 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable. 16. Patients with a known history of HIV seropositivity. 17. Patients with hypersensitivity to interferon alfa-2a or any component of the product. 18. Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism (>1 episode of DVT/PE during the past year). 19. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: ? unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ? 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ? 6 months before study treatment start ? severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air ? poorly controlled diabetes as defined by fasting serum glucose >2.0 x 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 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. 20. 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 uterine. 21. 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. 22. Patients who are using other investigational agents or who had received investigational drugs ? 4 weeks prior to study treatment start. 23. Patients unwilling to or unable to comply with the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS). Progression-free survival (PFS) is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. |
|
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 | 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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
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
| 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |