Estudio de fase 3b, aleatorizado y abierto de bevacizumab (Avastin®) + temsirolimus (Torisel®) frente a bevacizumab (Avastin®) + interferón alfa (Roferon®) como tratamiento de primera línea en pacientes con carcinoma de células renales avanzadoPhase 3b, Randomized, Open-Label Study of Bevacizumab (Avastin®) + Temsirolimus(Torisel®) vs. Bevacizumab (Avastin®) + Interferon-Alfa (Roferon®) as First-LineTreatment in Subjects With Advanced Renal Cell Carcinoma

Conditions: Tratamiento de primera línea en pacientes con carcinoma de células renales avanzadoFirst-Line Treatment in Subjects with Advanced Renal Cell Carcinoma

Registration Number: EUCTR2007-003793-26-ES

Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 800

Inclusion Criteria

1. Male or female subjects greater than or equal to 18 years.
2. Subject with histologically and/or cytologically confirmed, advanced (stage IV or recurrent) RCC, for whom a majority component of conventional clear-cell type is mandatory. (Subjects with predominantly papillary or sarcomatoid features, and subjects with chromophobe, oncocytoma, collecting duct tumors, Bellini tumors or transitional cell carcinoma are not allowed.)
3. At least 1 measurable lesion (per RECIST).
4. Karnofsky Performance Status greater than or equal to 70.
5. Screening laboratory values within the following parameters:
ANC: > or equal to 1.5 x 109/L (1500/mm3)
Platelet count: > or equal to 100 x 109/L (100,000/mm3)
Hemoglobin: > or equal to 8.0 g/dL (80g/L) without transfusion within 2 weeks of first dose of test article
Serum creatinine < or equal to 1.5 x upper limit of normal (ULN)
Total bilirubin < or equal to 1.5 x upper limit of normal (ULN)
AST and ALT < or equal to 2.5 x upper limit of normal (ULN) [< or equal to 5 x upper limit of normal (ULN) with liver metastases]
Fasting serum cholesterol < or equal to350 mg/dL (9.0 mmol/L)
Fasting serum triglycerides < or equal to 400 mg/dL (4.56 mmol/L)
HgbA1c < 10% (optimal therapy permitted)
INR and PTT < or equal to 1.5 (Anticoagulation is allowed if target INR <3 and INR is therapeutic on a stable dose of a coumarin type anticoagulation, or if the subject is on a stable dose of LMW heparin for >2 weeks at time of randomization.)
6. QTc interval < or equal to 450 msec for males and < or equal to 470 msec for females.
7. Life expectancy of at least 12 weeks.
8. Signed and dated institutional review board (IRB) or independent ethics committee (IEC) approved informed consent form before any protocol-specific screening procedures

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior systemic treatment for RCC in the neoadjuvant, adjuvant or metastatic setting. Prior treatment with bevacizumab, temsirolimus, sirolimus, IFN, sunitinib or sorafenib, for any indication.
2. Evidence of current or prior central nervous system (CNS) metastases or any imaging abnormality indicative of CNS metastases or spinal cord compression.
3. Major surgery (incl. open biopsy) or radiation therapy within 28 days prior to randomization. (Palliative radiotherapy to painful bone lesions is allowed within 14 days prior to randomization). Subject must have recovered from prior surgery and radiation.
4. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to randomization.
5. Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, II, or IV), angina pectoris requiring nitrate therapy, or myocardial infarction within the last 6 months;
6. Inadequately controlled hypertension (defined as a blood pressure of > or equal to 150 mmHg systolic and/or > or equal to 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy.
7. History of stroke or transient ischemic attack within 6 months prior to randomization
8. Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease
9. Known congenital long QT syndrome, history of torsades de pointes or ventricular tachycardia.
10. Known pulmonary hypertension or pneumonitis.
11. More than 1 episode of DVT/PE within the last 6 months.
12. Evidence or history of bleeding diathesis or coagulopathy.
13. Chronic daily aspirin >325 mg/day or clopidogrel (>75 mg/day)
14. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization
15. Any of the following serious, non-healing conditions: wound, ulcer, or bone fracture
16. Proteinuria at screening as demonstrated by either:
- Urine dipstick > or equal to 2+ (subjects discovered to have a > or equal to 2+ proteinuria on dipstick urinalysis at baseline should undergo 24-hour urine collection and must demonstrate < or equal to 1g of protein in 24 hours to be eligible.
- 24-hour urine collection demonstrates > or equal to 1g of protein in 24 hours.
17. Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus [anti HCV] with confirmatory testing. Note: Testing is not mandatory to be eligible for the study.)
18. Chronic treatment with corticosteroids (prednisone > or equal to 12.5 mg/day or dexamethasone > or equal to 2 mg/day) excluding inhaled steroids.
19. Pregnant or nursing women, women of childbearing potential not using a medically acceptable contraceptive method, or men not using a medically acceptable contraceptive method with partners of childbearing potential. A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant. Subjects (men and women) must agree to use medically accepted contraceptive methods for 12 weeks after the last dose of study drug.
20. Known hypersensitivity to any component of the test articles or excipients, or documented medical condition that would prohibit adequate pre-medication with antihistamine.
21. Current ac