Study of Interleukin-2, Interferon-alpha and Bevacizumab in Metastatic Kidney Cancer
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).
Metastatic Renal Cell Carcinoma
Drug: Interferon Alfa-2b
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- 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. ] [ Designated as safety issue: No ]
- 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). ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]
- Time to progression, (TTP) [ Time Frame: Time to progression is defined as time between date of randomisation and date of documented progression. ] [ Designated as safety issue: No ]
- Time to treatment failure, (TTTF) [ Time Frame: see below ] [ Designated as safety issue: No ]Time to treatment failure is defined as time between date of randomisation and date of insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawn informed consent.
- Tolerability [ Time Frame: see below ] [ Designated as safety issue: Yes ]Toxicity is recorded according to CTCAE v3.0
- Frequency of surgical resection of residual disease [ Time Frame: see below ] [ Designated as safety issue: No ]This is calculated as number of patients having surgical resection of residual disease compared with the total number of treated patients.
- Frequency of no evidence of disease (NED) [ Time Frame: see below ] [ Designated as safety issue: No ]This is calculated as the total number of patients having no evidence of disease as a result of CR to treatment, or as a result of PR/SD to treatment followed by surgical resection of residual disease, compared with the total number of treated patients.
- 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 ] [ Designated as safety issue: No ]
Blood tests and core biopsies from accessible tumor lesions will be obtained at baseline, after cycle 1 and at PD.
Blood analyses will include assessment of dendritic cells, FoxP3+ regulatory T-cells, NK-cells, T-subsets, neutrophils, monocytes, cytotoxic activity and antibody-dependent cellular cytotoxicity (ADCC).
Tumor analyses will include assessment of intratumoral immune cells, markers related to HIF accumulation and CD34+ microvessel density.
- To assess dynamic contrast-enhanced imaging as a potential biomarker. [ Time Frame: see below ] [ Designated as safety issue: No ]
Dynamic contrast-enhanced imaging (CT, MRI, and US) will be obtained at baseline, week 5 and at routine tumor assessments, if appropriate, for estimation of tumor blood perfusion change.
An exploratory analysis to identify any potential relationship between each of these assessments and outcome (progression free survival, survival, time to progression, response rate and safety) will be performed.
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|Experimental: Interleukin-2, interferon, bevacizumab||
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).
Other Name: Avastin
|Active Comparator: Interleukin-2 and interferon-alfa||
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).
Other Name: AldesleukinDrug: Interferon Alfa-2b
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.
Other Name: IntronA
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.
|Contact: Frede MD Donskov, DMSc||+45 email@example.com|
|Aarhus University Hospital||Recruiting|
|Aarhus, Denmark, 8000|
|Contact: Frede Donskov +4589493333 firstname.lastname@example.org|
|Sub-Investigator: Henrik Schmidt, MD, DMSc|
|Sub-Investigator: Kirsten Fode, MD|
|Sub-Investigator: Mads Agerbaek, MD|
|Herlev University Hospital||Recruiting|
|Herlev, Denmark, 2730|
|Contact: Poul Geertsen, MD, PhD +4544884488 POGE@heh.regionh.dk|
|Principal Investigator: Poul Geertsen, MD, PhD|
|Sub-Investigator: Lene Jarlbaek, MD, PhD|
|Principal Investigator:||Frede Donskov, MD, DMSc||Aarhus University Hospital|
|Study Chair:||Poul Geertsen, MD, PhD||University of Copenhagen|