A randomized, open label, multi-center phase II study to compare bevacizumab plus RAD001 versus interferon alfa-2a plus bevacizumab for the first-line treatment of patients with metastatic clear cell carcinoma of the kidney
- Conditions
- Patients with metastatic clear cell carcinoma of the kidneyMedDRA version: 14.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2008-000077-38-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
1. Age = 18 years old
2. Patients with metastatic renal cell carcinoma and with histological or
cytological confirmation of clear cell RCC (pathology report based on the
tissue from the original diagnosis or more recent biopsy of renal cell
cancer is acceptable). Any percentage of clear cell histology is
acceptable.
3. Patients with at least one measurable lesion at baseline as per the
RECIST criteria. If skin lesions are reported as target lesions, they must be documented (at baseline and at every physical exam) using color
photography and a measuring device (such as a caliper) in clear focus to
allow the size of the lesion(s) to be determined from the photograph.
4. Patients with progressive metastatic renal cell carcinoma.
Documentation of radiologically progressive disease by RECIST criteria is
required only in patients with lung and/or soft tissue metastases
without other sites of metastatic disease.
5. Patients who had a prior partial or complete nephrectomy. Partial
nephrectomy is allowed only if the resection margins were clearly
negative.
6. Patients with a Karnofsky Performance Status =70%.
7. Adequate bone marrow function as shown by: ANC = 1.5 x 109/L,
Platelets = 100 x 109/L, Hb >9 g/dL.
8. Adequate liver function: serum bilirubin: = 1.5 x ULN, ALT and AST =
2.5x ULN. Patients with known liver metastases: AST and ALT = 5x ULN.
9. Adequate renal function: serum creatinine = 2.0 x ULN.
10. INR < 1.5. (Anticoagulation is allowed if target INR = 1.5 on a stable
dose of warfarin or on a stable dose of LMW heparin for >2 weeks at
time of randomization.)
11. Women of childbearing potential must have had a negative serum
pregnancy test 72 hours prior to the administration of the study
treatment start.
12. Patients who give a written informed consent obtained according to
local guidelines..
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
1. Patients within 4 weeks post-major surgery, open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry.
2. Patients who had radiation therapy within 28 days prior to start of study treatment.
3. Patients in anticipation of the need for major surgical procedure during the course of the study.
4. Patients with a serious non-healing wound, ulcer, or bone fracture.
5. Patients with a history of seizure(s) not controlled with standard medical therapy.
6. Patients who have received prior systemic treatment for their metastatic RCC. Adjuvant immunotherapy (vaccines acceptable, but no cytokines) completed 3 months prior to study treatment start is acceptable.
7. Patients who received prior therapy with VEGF pathway inhibitor, such as sunitinib, sorafenib, and bevacizumab.
8. Patients who have previously received systemic mTOR inhibitors.
9. Patients with a known hypersensitivity to RAD001 or other rapamycins or to its excipients.
10. Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression.
11. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
12. Patients with proteinuria at screening as demonstrated by either:
• Urine protein: creatinine (UPC) ratio = 1.0 at screening.
• Urine dipstick for proteinuria = 2+ (patients discovered to have =2+
proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible).
13. Patients with inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 100 mmHg diastolic medication), or any prior history of hypertensive crisis or hypertensive encephalopathy.
14. Patients receiving ongoing or with recent (within 10 days prior to study treatment start) need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin (> 325
mg/day) or clopidogrel (>75 mg/day).
15. Patients receiving chronic systemic treatment with corticosteroids (dose of = 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable.
16. Patients with a known history of HIV seropositivity.
17. Patients with hypersensitivity to interferon alfa-2a or any component of the product.
18. Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism (>1 episode of DVT/PE during the past year).
19. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• unstable angina pectoris (at any time), symptomatic congestive heart failure (NYHA II, III, IV) (at any time), serious uncontrolled cardiac
arrhythmia (at any time), myocardial infarction or cerebrovascular accidents = 6 months prior to first study treatment or history of left ventricular dysfunction
• severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN
• any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method