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

December 1, 2014 updated by: University of Aarhus

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

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

118

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • Aarhus University Hospital
      • Herlev, Denmark, 2730
        • Herlev University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • IntronA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 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.
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.
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 progression is defined as time between date of randomisation and date of documented progression.
Time to treatment failure, (TTTF)
Time Frame: see below
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.
see below
Tolerability
Time Frame: see below
Toxicity is recorded according to CTCAE v3.0
see below
Frequency of surgical resection of residual disease
Time Frame: see below
This is calculated as number of patients having surgical resection of residual disease compared with the total number of treated patients.
see below
Frequency of no evidence of disease (NED)
Time Frame: see below
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.
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

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.
see below
To assess dynamic contrast-enhanced imaging as a potential biomarker.
Time Frame: see below

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.
see below

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

Danish Renal Cancer Study Group

Investigators

  • Principal Investigator: Frede Donskov, MD, DMSc, Aarhus University Hospital
  • Study Chair: Poul Geertsen, MD, PhD, University of Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (ANTICIPATED)

December 1, 2015

Study Completion (ANTICIPATED)

December 1, 2015

Study Registration Dates

First Submitted

June 29, 2010

First Submitted That Met QC Criteria

January 10, 2011

First Posted (ESTIMATE)

January 11, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

December 2, 2014

Last Update Submitted That Met QC Criteria

December 1, 2014

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DARENCA-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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