A comparison of blood and tissue biomarkers before and after nephrectomy in the firstline setting with everolimus in patients with locally advanced or metastatic renal cell carcinoma

Phase 1

Conditions: locally advanced or metastatic renal cell carcinoma - 1st line
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-000882-11-FR

Lead Sponsor: A.R.T.I.C. (Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie )

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

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 < 5 mmol/L, triglycerides < 200 mg/dl, blood glucose < 1.5x
ULN
9. Negative pregnancy test within 7 days prior to enrollment
10. Signed and dated IRB/ICE-approved informed consent form
11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures.
12. Patient covered by the national health system
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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.