| 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 |
|
| 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 | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10038409 |
| E.1.2 | Term | Renal cell carcinoma NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 objective of the study is to assess the efficacy of everolimus in patients with metastatic renal cell cancer whose disease progressed on or after prior first-line treatment with sunitinib or pazopanib. Efficacy will be measured by the rate of patients who are free of disease progression after 6 months of treatment with everolimus. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to gather additional data on the efficacy and safety of everolimus in patients after prior treatment with sunitinib or pazopanib. To this end, the following will be evaluated:
Estimate the progression-free survival of patients treated with everolimus after having progressed on or after first-line sunitinib or pazopanib therapy
To assess overall survival of patients treated with everolimus after failure of first-line sunitinib or pazopanib therapy
To assess overall response rate (ORR) according to RECIST-criteria (version 1.1) after failure of first-line sunitinib or pazopanib therapy
To assess the duration of response after failure of first-line sunitinib or pazopanib therapy
To assess the safety profile of everolimus after failure of first-line sunitinib or pazopanib therapy
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell renal carcinoma.
2. Progression during or after a treatment with sunitinib or pazopanib given in a 1st line treatment situation for mRCC.
3. Patients scheduled for treatment with everolimus (Afinitor®).
4. Patients with at least one measurable lesion at baseline as per RECIST-criteria version 1.1.
5. Patients with ECOG PS 0-1.
6. Absolute neutrophile count ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hb > 9 g/dL (5.6 mmol/l).
7. serum bilirubin: ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases: AST and ALT ≤ 5x ULN.
8. serum creatinine ≤ 2.5 x ULN.
9. Urine protein of < 2+ in dip stick testing.
10. Patients able to give written informed consent.
11. Age ≥18 years old.
|
|
| E.4 | Principal exclusion criteria |
1. Patients who have received >1 prior systemic treatment for their metastatic RCC. Prior systemic treatment in an adjuvant setting is allowed.
2. Patients who have previously received systemic mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus).
3. Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
4. Patients within 4 weeks post-major surgery (e.g. intra-thoracic, intra-abdominal or intrapelvic), open biopsy or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device 7 days prior to study entry.
5. Patients who have had radiation therapy within 4 weeks prior to start of study treatment. Palliative radiotherapy to bone lesions within 2 weeks prior to study treatment start.
6. History or clinical evidence of central nervous system (CNS) metastases. Subjects who have previously treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
o are asymptomatic
and
o have had no evidence of active CNS metastases for ≥ 3 months prior to enrolment (inactive/controlled CNS metastases are allowed)
and
o have no requirement for steroids or enzyme-inducing anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin)
7. Patients in anticipation of the need for major surgical procedure during the course of the study.
8. Patients with a serious non-healing wound, ulcer or bone fracture.
9. Patients with a history of seizure(s) not controlled with standard medical therapy.
10. Patients receiving chronic systemic treatment with corticosteroids (dose of >10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable.
11. Severely impaired lung function with a resting 02-saturation that is 88% or less on room air.
12. Poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN.
13. Impaired liver function classified as Child-Pugh class A, B, or C.
14. Active (acute or chronic) or uncontrolled infection of bacterial, mycotic or viral genesis.
15. Liver disease such as chronic active hepatitis or chronic persistent hepatitis.
16. Patients with positive history of severely impaired renal function or prior diagnosis of renal failure or proteinuria.
17. Patients with a known history of HIV seropositivity.
18. Patients with active bleeding.
19. Patients who have any severe and/or uncontrolled medical conditions that could affect their participation in the study, e.g. uncontrolled hypertension defined as systolic blood pressure >160 mmHg and/ or diastolic blood pressure >90 mmHg.
20. Patients who have a history of another primary malignancy and of 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) or prostate (T1 - T2).
21. Female patients who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)), or adults of reproductive potential who are not using effective birth control methods (Pearl Index <1). If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Oral contraceptives that do not contain estrogen are acceptable for female patients. Other oral contraceptives are not acceptable because of possible interactions with the study treatment which might lead to failure of the oral contraceptive. All oral contraceptives are allowed for female partners of a male patient.
22. Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
23. Patients unwilling or unable to comply with the protocol.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this study is to evaluate the efficacy of everolimus (Afinitor®) in patients with progressive renal cell carcinoma after failure of first-line sunitinib or pazopanib therapy. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| The secondary efficacy objectives are to evaluate progression-free survival (PFS), overall survival (OS), duration of response (CR/PR) and overall response rate (CR/PR). If not otherwise indicated, secondary efficacy variables will be analyzed for the FAS using radiologic assessments. Frequencies will be reported for proportions together with exact confidence intervals computed according to the Clopper-Pearson method. Time-to-event variables will be analyzed using the Kaplan-Meier method. Kaplan-Meier estimates will be presented together with appropriate confidence intervals. Furthermore, 25%, 50% (median time-to-event) and 75% percentiles will be displayed. The Kaplan-Meier curve will be presented graphically. For convenience, for all secondary efficacy analyses, two-sided 95% confidence intervals will be provided. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 6 months; overall survival after 4 years |
|
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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.8.2.4 | 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 | 12 |
| 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 | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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 | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
Print
