Patient with previously untreated Metastatic Renal Cell Carcinoma MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma
Conditions
Sponsors
Department of Oncology, Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent obtained prior to any study specific screening procedures. 2. Patient must be willing and able to comply with the protocol. 3. Age ? 18. 4. Histologic og cytologic biopsy proven locally advanced or metastatic renal cell carcinoma, considered non-candidates for curative surgery. Nephrectomy is not mandatory. 5. Patient with renal cell carcinoma (RCC) with a clear-cell histologic component confirmed by local pathology review. (Patient with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumours, Bellini tumours and transitional cell carcinoma are not allowed.) 6. If metastatic disease is diagnosed more than two years from the date of the initial diagnosis of RCC, histological or cytological confirmation of renal cell carcinoma (clear cell type) origin of the metastatic lesion(s) is mandatory. 7. Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating. 8. Fertile women of childbearing potential (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior systemic treatment for metastatic RCC disease (including neo-adjuvant therapy). 2. Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to randomization. 3. Serious non-healing wound, ulcer or bone fracture. 4. Evidence of current central nervous system (CNS) metastases or spinal cord compression. Patient must undergo an MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to randomization. 5. Seizure(s) not controlled with standard medical therapy. 6. Dipstick urine test of protein = 2+. 7. Other malignancies within 5 years prior to randomization (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix). 8. Evidence of bleeding diathesis or coagulopathy. 9. Ongoing or recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral anticoagulants or chronic daily treatment with aspirin. Low molecular weight heparin are allowed 10. Uncontrolled hypertension (? 160 mm Hg systolic and/or ? 100 mm Hg diastolic) while receiving chronic medication. 11. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (= 6 months before randomisation), myocardial infarction (= 6 months before randomisation), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication. 12. Recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study. 13. Chronic treatment with corticosteroids (dose of = 10 mg/day methylprednisolone equivalent), excluding inhaled steroids. 14. History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications. 15. Known hypersensitivity to interleukin-2, Inferferon, alpha or bevacizumab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Avastin as monotherapy has effect in mRCC. Avastin in combination with interferon-alfa (IFN-a) has significant efficacy in mRCC and has been approved by EMEA. The present study will assess whether the combination of Interleukin-2 (IL-2) and IFN-a with Avastin may add efficacy in patients with mRCC with a tolerable safety profile. Progression Free Survival;Secondary Objective: Response rate, overall survival (OS), duration of response, time to progression, time to treatment failure, tolerability, frequency of surgical resection of residual disease and frequency of no evidence of disease (NED). To explore the immunomodulatory effect of therapy in serial blood samples and serial tumor core biopsies and to correlate these biomarkers with outcome. To assess dynamic contrast-enhanced imaging as a potential biomarker;Primary end point(s): Primary objective • To determine the efficacy of the combination of interleukin-2 / interferon alfa-2b plus bevacizumab as compared with interleukin-2 /interferon-alfa 2b in patients with metastatic RCC, based on progression free survival (PFS). | — |
Countries
Denmark
Outcome results
None listed