A Randomized Phase II Trial of IL-2/IFN-α Plus Bevacizumab Versus IL-2/IFN-α in Metastatic Renal Cell Carcinoma (mRCC) - Danish Renal Cancer Group (DARENCA) Study-1
1. Signed written informed consent
2. Patient must be willing and able to comply with the protocol.
3. Age ≥ 18 years.
4. Histologic og cytologic biopsy proven locally advanced or metastatic renal cell
carcinoma, considered non-candidates for curative surgery. Nephrectomy is not
5. Patient with renal cell carcinoma (RCC) with a clear-cell histologic component
confirmed by local pathology review.
6. Females with a negative serum pregnancy test unless childbearing potential can be
7. Fertile women of childbearing potential (<2 years after last menstruation) and men
must use effective means of contraception
8. Memorial-Sloan-Kettering-Cancer-Centre favourable- and intermediate prognostic group.
9. Measurable or non-measurable disease (as per RECIST1.1 criteria)
10. Karnofsky Performance status of 70% or higher.
11. Life expectancy greater than 4 months.
12. The required laboratory values at baseline are as follows:
WCC ≥ 3.0 x 109/L, Platelet count ≥ 100 x 109/L, Haemoglobin ≥ 6.2 mmol/l, (INR) ≤ 1.5,
APTT ≤ 1.5 x ULN
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 ≤
1. Prior systemic treatment for metastatic RCC disease
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
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, Interferon, alfa or bevacizumab.
Serial blood test, serial tumor biopsies and serial dynamic contrast-enhanced imaging will
be obtained as part of a translational research program integrated in the clinical trial.
Part(s) of the translational research program may be omitted in the individual patient due
to practical, technical or safety reasons, without having consequences for participating
in the additional translational research investigations or the clinical part of the study.