E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients who have metastatic papillary cancer of the kidney and have not received prior systemic treatment for their metastatic RCC. This multicenter international trial will enroll a maximum of 60 patients over a period of approximately 12 months. |
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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 efficacy of everolimus as monotherapy for the treatment of papillary renal cancer. Efficacy is defined as the percentage of patients progression-free at 6 months. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the response rate, duration of response, disease control rate, median progression free survival and overall survival in this patient population, and to further characterize the safety profile of everolimus. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years old • Patients with histological diagnosis of metastatic papillary renal cell carcinoma, type I or II, centrally confirmed (relevant slides (and blocks if available) must be sent for central reading within one month from enrollment: if this is not feasible the patient cannot be considered eligible) • Patients with at least one measurable lesion at baseline as per RECIST criteria • Patients with an ECOG performance status of ≤ 1 • 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 as shown by: serum bilirubin: ≤ 1.5 x ULN, INR< 1.3 (or <3 on anticoagulants), ALT and AST ≤ 2.5x ULN. For patients with known liver metastases: AST and ALT ≤ 5x ULN. • Adequate renal function as shown by: serum creatinine ≤ 2.0 x ULN. • Life expectancy ≥ 3 months • Fasting serum cholesterol ≤300 mg/dL or ≤7.5 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. • Women of childbearing potential must have had a negative urine or blood pregnancy test within one week prior to the administration of the study treatment start. • Patients who give a written informed consent obtained according to local guidelines. |
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E.4 | Principal exclusion criteria |
• 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). • Patients who have received any prior systemic treatment for their metastatic RCC, such as sunitinib, sorafenib, and bevacizumab. • Patients who have previously received mTOR inhibitors (sirolimus, temsirolimus, everolimus). • Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients. • Patients with uncontrolled central nervous system (CNS) metastases. • Patients receiving chronic systemic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable, as well as opotherapy after bilateral adrenal gland removal. • Patients with a known history of HIV seropositivity. • Patients with autoimmune hepatitis. • Patients with an active, bleeding diathesis. • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study • 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. • 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. • Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start. • Patients unwilling or unable to comply with the protocol. • Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients progression-free at month 6 |
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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 | 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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 2 |
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 | 2 |