E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Renal Cell Carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Metastatic Renal Cell Carcinoma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
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 |
To assess the progression-free survival (PFS) in patients who receive
everolimus as second-line treatment for metastatic renal cell carcinoma |
|
E.2.2 | Secondary objectives of the trial |
- To assess the safety profile of everolimus for the overall study
population as well as for each first-line treatment cohort
- To assess the progression-free survival (PFS) separately for each firstline treatment cohort
- To assess the overall survival (OS) for patients treated with secondline therapy with everolimus, as well as for each first-line treatment cohort
- To assess the clinical benefit rate and duration of response in patients who receive everolimus in second-line setting, as well as for each firstline treatment cohort |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Advanced renal cell carcinoma of a histological or cytological confirmation of clear cell (or with a component of clear cell) renal carcinoma that have previously progressed on or were intolerant to firstline therapy with sunitinib, sorafenib, pazopanib, axitinib, bevacizumab, or cytokine therapy
- Prior nephrectomy (partial or total)
- Patients with at least one measurable lesion at baseline as per the RECIST 1.0 criteria
- Karnofsky Performance Status ≥ 70%
- Age ≥ 18 years old
Other protocol-defined inclusion criteria may apply. |
|
E.4 | Principal exclusion criteria |
- Patients who have received more than one prior treatment regimen for metastatic renal-cell carcinoma
- Patients who have received adjuvant therapy for RCC
- Patients who have previously received systemic mTOR inhibitors (eg, sirolimus, temsirolimus, everolimus)
- Patients with brain metastases
- Patients within 4 weeks post-major surgery, open biopsy, or significant traumatic injury to avoid wound healing complications.
- Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed up to 2 weeks prior to study treatment start).
- Concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
Other protocol-defined exclusion criteria may apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival in patients who receive everolimus as secondline treatment for metastatic renal cell carcinoma |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
every 8 weeks until the occurrence of documented disease progression
per RECIST 1.0 |
|
E.5.2 | Secondary end point(s) |
1- Safety profile of everolimus for the overall study population as well as
for each first-line treatment cohort.
2- Progression-free survival separately for each first-line treatment
cohort
3- Overall survival
4- Clinical benefit rate
5- Objective response rate
6- Duration of response |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Continuously
2- Every 8 weeks until the occurrence of documented disease
progression per RECIST 1.0
3- Continuously
4- Every 8 weeks until the occurrence of documented disease
progression per RECIST 1.0
5- Every 8 weeks until the occurrence of documented disease
progression per RECIST 1.0
6- Every 8 weeks until the occurrence of documented disease
progression per RECIST 1.0 |
|
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | No |
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 |
Argentina |
Brazil |
Bulgaria |
China |
India |
Romania |
Russian Federation |
United States |
|
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
|
Patients will be treated until the occurence of documented disease
progression, or discontinuation due to unacceptable toxicity or for
other reasons. |
|
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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |