This trial is active, not recruiting.

Condition metastatic renal cell carcinoma
Treatments interleukin-2, interferon alfa-2b, bevacizumab
Phase phase 2
Target VEGF
Sponsor University of Aarhus
Collaborator Danish Renal Cancer Study Group
Start date October 2009
End date December 2015
Trial size 118 participants
Trial identifier NCT01274273, DARENCA-1


The purpose of this study is to determine whether interleukin-2, interferon-alpha in combination with bevacizumab are effective in the treatment of metastatic renal cell carcinoma (mRCC).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
bevacizumab Avastin
Bevacizumab doses of 10 mg per kilogram of body weight, given every two weeks i.v. until disease progression, unacceptable toxicity, withdrawal of consent or a maximum of 1 year following obtaining no evidence of disease (NED).
(Active Comparator)
interleukin-2 Aldesleukin
2.4 MIU/m2 s.c. two times daily, 5 days per week, weeks 1 and 2, every 28-day-cycle, for a maximum of 9 cycles (i.e.for a maximum of 9 months).
interferon alfa-2b IntronA
IFN-alfa given as one priming-week of daily IFN 3.0 MIU, followed by up to 9 treatment cycles (i.e. for a maximum of 9 months) with IFN-alfa 3.0 MIU as a fixed dose s.c. once daily - 5 days per week.

Primary Outcomes

Progression free survival, PFS
time frame: This is defined as the time between date of randomisation and the first date of documented disease progression or date of death due to any cause.

Secondary Outcomes

Response rate, RR
time frame: Overall response rate as assessed by the RECIST 1.1 criteria. An overall response is defined as a confirmed complete response (CR) or confirmed partial response (PR).
Overall survival, (OS)
time frame: Overall survival is defined as the time between date of randomisation and the date of death due to any cause.
Duration of response
time frame: Duration of response is defined as the time between the date a response (CR or PR) was first seen until date of progression.
Time to progression, (TTP)
time frame: Time to progression is defined as time between date of randomisation and date of documented progression.
Time to treatment failure, (TTTF)
time frame: see below
time frame: see below
Frequency of surgical resection of residual disease
time frame: see below
Frequency of no evidence of disease (NED)
time frame: see below
To explore the immunomodulatory effect of therapy in serial blood samples and serial tumor core biopsies and to correlate these biomarkers with outcome
time frame: see below
To assess dynamic contrast-enhanced imaging as a potential biomarker.
time frame: see below

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 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 mandatory. 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 otherwise excluded 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: Haematology: 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 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 ≤ 150 micromol/L - Exclusion Criteria: 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 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, 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. -

Additional Information

Official title 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
Principal investigator Frede Donskov, MD, DMSc
Description Bevacizumab as monotherapy has effect in metastatic renal cell carcinoma (mRCC). Bevacizumab in combination with interferon-alfa (IFN-α) has significant efficacy in mRCC and has been approved by EMA and FDA. The present study will assess whether the combination of Interleukin-2 (IL-2) and IFN-α with bevacizumab may add efficacy in patients with mRCC with a tolerable safety profile.
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by University of Aarhus.