A randomised, double-blind phase III study to evaluate the efficacy and safety of bevacizumab in combination with interferon alfa-2a (Roferon) versus interferon alfa-2a and placebo as first line treatment administered to nephrectomised patients with metastatic clear cell renal cell carcinoma. PK Substudy: BE, FR, HU, IT & UK only - Study of Pharmacokinetic Interaction between Bevacizumab and Interferon alpha-2a (Roferon-A) in Patients with Metastatic Clear Cell Renal Cell Carcinoma.

Phase 1

Conditions: Metastatic clear cell renal cell carcinoma
MedDRA version: 7 Level: PT Classification code 10038415

Registration Number: EUCTR2004-000282-35-GB

Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 638

Inclusion Criteria

1. Signed written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures.
2. Patient must be willing and able to comply with the protocol.
3. Age 18 or over.
4. Patient was nephrectomised for primary renal cell carcinoma (clear cell type). Partial nephrectomy is allowed only if the resection margins were clearly negative.
5. Patient with renal cell carcinoma (RCC) for whom a majority component (> 50%) of conventional clear cell type is mandatory. (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). 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.
6. Females with a negative serum pregnancy test (to be confirmed by urine test if serum test was performed more than 7 days prior to the treatment start) unless childbearing potential can be otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating.
7. Fertile women (<2 years after last menstruation) and men of childbearing potential must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgical sterilisation).
8. Measurable or non-measurable disease (as per RECIST criteria).
9. Karnofsky Performance status equal to or greater than 70%.
10. Life expectancy greater than 4 months.
11. Absence of proteinuria at baseline as defined by < 0.5 g of protein/24 hr on mandatory 24-hour urine collection.
12.The required laboratory values at baseline are as follows:
Haematology:
Absolute neutrophil count (ANC) = 1.5 x 10(9)/L, Platelet count = 100 x 10(9)/L, Haemoglobin = 9 g/dL (may be obtained or exceeded by the use of erythropoietin, excluding transfusion for anaemia), International Normalized Ratio (INR) = 1.5, aPTT = 1.5 x ULN
Biochemistry:
Total bilirubin = 1.5 x upper limit of normal (ULN), AST, ALT = 2.5 x ULN in patients without liver metastases, = 5 x ULN in patients with liver metastases, Serum Creatinine = 2.0 mg/dL or = 177 micromol/L

PK substudy:
- Patients having received, prior to the PK visit, three infusions of bevacizumab (or placebo) dosed at 10mg/kg at two weekly intervals.
- Patients having received interferon alpha-2a treatment at a dose regimen stable over the two weeks prior to treatment cycle =4.

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 metastatic RCC disease (including neo-adjuvant therapy).
2. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
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 randomisation.
5. Seizure(s) not controlled with standard medical therapy.
6. Other malignancies within 5 years prior to randomisation (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
7. Evidence of bleeding diathesis or coagulopathy.
8. Ongoing or 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).
9. Uncontrolled hypertension (greater than or equal to 160 mm Hg systolic and/or greater than or equal to 90 mm Hg diastolic) while receiving chronic medication.
10. 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.
11. Recent (within the 30 days prior to randomisation) treatment with another investigational drug or participation in another investigational study.
12. Chronic treatment with corticosteroids (dose of =10 mg/day methylprednisolone equivalent), excluding inhaled steroids.
13. 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.

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

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