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Study of Interleukin-2, Interferon-alpha and Bevacizumab in Metastatic Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by University of Aarhus
Sponsor:
Collaborator:
Danish Renal Cancer Study Group
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01274273
First received: June 29, 2010
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

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).


Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Drug: Interleukin-2
Drug: Interferon Alfa-2b
Drug: Bevacizumab
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 118
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)
Arms Assigned Interventions
Experimental: Interleukin-2, interferon, bevacizumab Drug: 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 Drug: Interleukin-2
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: Aldesleukin
Drug: 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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01274273

Contacts
Contact: Frede MD Donskov, DMSc +45 89493333 frede.donskov@aarhus.rm.dk

Locations
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8000
Contact: Frede Donskov    +4589493333    frede.donskov@aarhus.rm.dk   
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         
Sponsors and Collaborators
University of Aarhus
Danish Renal Cancer Study Group
Investigators
Principal Investigator: Frede Donskov, MD, DMSc Aarhus University Hospital
Study Chair: Poul Geertsen, MD, PhD University of Copenhagen
  More Information

No publications provided

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01274273     History of Changes
Other Study ID Numbers: DARENCA-1
Study First Received: June 29, 2010
Last Updated: August 30, 2012
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by University of Aarhus:
Bevacizumab
interleukin-2
interferon-alpha

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Bevacizumab
Interferon-alpha
Interferons
Interleukin-2
Analgesics
Analgesics, Non-Narcotic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Central Nervous System Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014