locally advanced or metastatic renal cell carcinoma - 1st line
Conditions
Interventions
Trade Name: everolimus
Product Name: Afinitor
Product Code: L01XE10
Pharmaceutical Form: Tablet
Sponsors
A.R.T.I.C. (Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie )
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with advanced RCC or a resectable renal tumor and at least one measurable inoperable metastasis (³1 cm), in whom anti-angiogenic therapy is indicated 2. Patients without target lesions, with bone metastasis 3. Histologically confirmed clear cells RCC (biopsy) and possibility of adequate tumor sampling prior to treatment 4. No prior systemic treatment for RCC 5. Male or female, 18 years 6. Performance status ECOG 0-1 7. Life expectancy 3 months 8. Adequate organ function as defined by the following criteria: - Total serum bilirubin £ 2 x ULN (Gilbert’s disease exempted) - Serum transaminases and alkaline phosphatases £2.5 x ULN, or in case of liver or bone metastasis £ 5x ULN - Serum creatinine £ 2 x ULN, creatinine clearance ³ 50 ml/min - Absolute neutrophil count (ANC) ³ 1500/mm3 - Platelets ³ 100,000/mm3 - Hemoglobin ³ 10.0 g/dL - INR £ 1.7 or prothrombin time (PT) £ 6 sec - Fasting cholesterol =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Previous nephrectomy 2. Histology: Renal collecting duct carcinoma 3. Treatment in a clinical trial in the last 30 days 4. Previous treatment with everolimus or other mTOR-inhibitors and anti-angiogenic drugs 5. Any of the following within 12 months prior to treatment initiation: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, ischemic or hemorrhagic stroke including transient ischemic attack. 6. Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical treatment 7. Ongoing cardiac dysrhythmia of grade ³ 2, atrial fibrillation of any grade, QTc interval > 0.45 8. Treatment with anticonvulsant agents and vitamin K antagonists. Ongoing treatment with therapeutic doses of coumarin derivative anticoagulants (e.g. warfarin) or treatment within the 2 weeks before the first day of everolimus administration. Prophylaxis with low dose warfarin for deep vein thrombosis is permitted (up to 2 mg/day). Low molecular weight heparin is allowed. 9. Any medical condition that might interfere with the absorption of oral medication. 10. Brain metastasis. (Note: Brain scan or MRI is mandatory). 11. Left ventricular ejection fraction (LVEF) value < 50% as assessed by echocardiography or multigated acquisition (MUGA) scan. 12. Pregnancy or breastfeeding. Women and men must agree to use effective contraception during the study period. Acceptable contraception includes implants, oral contraceptives, intrauterine devices, and surgical sterilization. 13. Any acute or chronic medical or psychiatric condition or laboratory abnormality that would make the patient unsuited to study participation. 14. Any second malignancy within the last 5 years with the exception of basal cell carcinoma, in situ cervical cancer and pT1/a bladder cancer with no evidence of recurrent disease for 12 months. 15. Clinically significant gastrointestinal abnormalities including but not limited to: a. Malabsorption syndrome b. Major resection of the stomach or small bowel that could affect the absorption of the study drug c. Active peptic ulcer disease d. Inflammatory bowel disease e. Ulcerative colitis or other gastrointestinal conditions with increased risk of perforation f. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment g.Hépatite B/C 16. Hypersensitivity to everolimus or any excipient of everolimus.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the prognostic value of several factors in order to identify responders to treatment: - Tumor biomarkers - Blood biomarkers - DCE-CT scan imaging at 4 weeks after treatment initiation.;Secondary Objective: 1) To determine the objective response of the primary tumor to everolimus treatment (using RECIST criteria). 2) To assess tumor response (tumor cell spread), Progression Free Survival (PFS) as defined by the progression of metastases, and overall survival (OS). 3) To correlate tumor cell spread (as determined by the pathologist) and tumor size reduction (as measured by CT scan) between treatment initiation and nephrectomy. 4) To compare biomarker expression in the pre-treatment biopsy and in the primary tumor surgical specimen after 6 weeks of treatment. 5) To determine whether the study biomarkers have prognostic value in regard to tumor response and PFS. 6) Safety Evaluation of Everolimus according to NCI-CTC version 4.0, including pulmonary toxicity.;Primary end point(s): To evaluate the prognostic value of several factors in order to identify responders to treatment: - Tumor biomarkers - Blood biomarkers - DCE-CT scan imaging at 4 weeks after treatment initiation.;Timepoint(s) of evaluation of this end point: Tumor biomarkers: at biopsy and at nephrectomy Blood biomarkers: day 28 of cycle 1 (week 4), day 1 of cycle 2 (week 6), day 28 of cycle 2 (week 10), just before everolimus introduction after nephrectomy (week 14), 3 months post nephrectomy (week 26 / J1 of cycle 5) and if possible at tumor progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Pathological response - Progression-Free Survival (PFS) - Overall survival (OS) - Objective clinical benefit (defined as CR+PR+SD) - Treatment duration - Time to response;Timepoint(s) of evaluation of this end point: Objective clinical benefit (defined as CR+PR+SD) will be measured on the primary tumor at W6 according to RECIST criteria version 1.1. After radical nephrectomy, clinical benefit will be evaluated every 8 weeks on metastases. To study the correlation between clinical benefit and tumor response, data on the following will be collected: - Change in tumor size: difference in primary tumor size at 6W (just before radical nephrectomy) - Pathological response: tumor cell spread within tumor tissue. A complete pathological response will be obtained if fewer than 10% of tumor cells are detected by the anatomopathologist in tumor tissue. - PFS: time from treatment initiation to first documentation of objective tumor progression or death. - OS: time from treatment initiation to death. | — |
Countries
France
Contacts
Public ContactSponsor
A.R.T.I.C. (Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie )
Outcome results
None listed