E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically confirmed advanced Renal Cell Carcinoma, with non-clear cell pathology. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038389 |
E.1.2 | Term | Renal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary endpoint will be a comparison of progression-free survival (PFS) between the treatment arms following therapy initiation. Disease progression is defined by documentation of progressive disease, a new primary malignancy, or death (whichever occurs first), censored at the last tumor evaluation date. |
|
E.2.2 | Secondary objectives of the trial |
• 6-, 12- and 24-month rates of PFS i • (PFS) expressed compared to an historic control • compare the overall response rate • Compare Stable Disease and Clinical Benefit Rate • Compare overall survival (OS) rates • Compare the best tumor shrinkage • Correlate clinical measures of response and PFS with baseline and time-dependent levels of biomarkers. • Evaluate ichanges in copy number, RNA expression, and immunohistochemical profiles between primary non-clear cell RCC tumors and metastatic samples. • Compare the median duration of response • Compare the median OS • Compare the time-to-new metastatic disease in each treatment arm • Compare change in quality-of-life • Assess toxicities associated with everolimus or sunitinib
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed advanced RCC, with non-clear cell pathology. Pathology must consist predominantly (> 50%) of papillary or chromophobe or undifferentiated histology. Mixtures of these non-clear cell variants are allowed. 2. RCC tumor tissue available for correlative sciences, from either primary or metastatic site or both. 3. At the time of screening, at least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3.0) Grade ≤ 1. 4. Subject must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1.1 criteria |
|
E.4 | Principal exclusion criteria |
1. subjects with a history of or active central nervous system (CNS) metastases. CNS metastases are allowed provided they have been treated and have been stable without new or growing lesions for 6 weeks. 2. Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy, chemotherapy, biologic or experimental therapy. 3. Collecting duct, medullary, small cell, oncocytoma, or lymphoma-type pathology is not allowed. Sarcomatoid variants of papillary or chromophobe carcinoma is permitted but not if clear cell features are predominant (>50% involvement). 4. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. Subjects on acceptable CYP3A4 isoenzyme inhibitors and/or inducers are eligible, provided they have been taking a stable regimen for at least 4 weeks prior to screening. 5. Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit. 6. Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be a comparison of the rate of progression-free survival (PFS) between the treatment arms at 6 months following therapy initiation. |
|
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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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 | No |
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 | 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
|
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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |