AzTrials
AzTrials

Metastatic Renal Cell CarcinomaPhase 2NCT01274273

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

A Phase 2 study testing Interleukin-2, Interferon Alfa-2b and Bevacizumab in people with Metastatic Renal Cell Carcinoma, run by University of Aarhus at 2 sites in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Interleukin-2, Interferon Alfa-2b and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
2 sitesDenmark
Study dates
Oct 2009to Dec 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • Patient must be willing and able to comply with the protocol.
  • Age ≥ 18 years.
  • Histologic og cytologic biopsy proven locally advanced or metastatic renal cell carcinoma, considered non-candidates for curative surgery. Nephrectomy is not mandatory.
  • Patient with renal cell carcinoma (RCC) with a clear-cell histologic component confirmed by local pathology review.
  • Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded
Show all 17Show fewer
  • Fertile women of childbearing potential (<2 years after last menstruation) and men must use effective means of contraception
  • Memorial-Sloan-Kettering-Cancer-Centre favourable- and intermediate prognostic group.
  • Measurable or non-measurable disease (as per RECIST1.1 criteria)
  • Karnofsky Performance status of 70% or higher.
  • Life expectancy greater than 4 months.
  • 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
  • -

Who cannot join

  • Prior systemic treatment for metastatic RCC disease
  • Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to randomization.
  • Serious non-healing wound, ulcer or bone fracture.
  • 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.
  • Seizure(s) not controlled with standard medical therapy.
  • Dipstick urine test of protein ≥ 2+.
Show all 18Show fewer
  • 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).
  • Evidence of bleeding diathesis or coagulopathy.
  • 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
  • Uncontrolled hypertension (≥ 160 mm Hg systolic and/or ≥ 100 mm Hg diastolic) while receiving chronic medication.
  • 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.
  • Recent (within the 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
  • Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent), excluding inhaled steroids.
  • 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.
  • 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.
  • -

Trial locations and contacts

2 sites in 1 country.

Denmark2 sites

  • Aarhus University Hospital

    Aarhus, Aarhus, 8000

  • Herlev University Hospital

    Herlev, Herlev, 2730

Other trials in Denmark

About this study

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

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).

Read the 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.

Being tested
Interleukin-2, Interferon Alfa-2b, Bevacizumab
Keywords
Bevacizumab, interleukin-2, interferon-alpha
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interleukin-2Drug

    Also called 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-2bDrug

    Also called 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.

  • BevacizumabDrug

    Also called 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).

Study groups in NCT01274273
Study groupRoleWhat they receive
Interleukin-2, interferon, bevacizumabExperimentalNot described
Receives: Drug: Bevacizumab
Interleukin-2 and interferon-alfaActive comparatorNot described
Receives: Drug: Interleukin-2; Drug: Interferon Alfa-2b

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival, PFS

    Measured: 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 (10)

  1. Response rate, RR

    Measured: 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).

  2. Overall survival, (OS)

    Measured: Overall survival is defined as the time between date of randomisation and the date of death due to any cause.

  3. Duration of response

    Measured: Duration of response is defined as the time between the date a response (CR or PR) was first seen until date of progression.

  4. Time to progression, (TTP)

    Measured: Time to progression is defined as time between date of randomisation and date of documented progression.

  5. Time to treatment failure, (TTTF)

    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.

    Measured: see below

  6. Tolerability

    Toxicity is recorded according to CTCAE v3.0

    Measured: see below

  7. Frequency of surgical resection of residual disease

    This is calculated as number of patients having surgical resection of residual disease compared with the total number of treated patients.

    Measured: see below

  8. Frequency of no evidence of disease (NED)

    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.

    Measured: see below

  9. To explore the immunomodulatory effect of therapy in serial blood samples and serial tumor core biopsies and to correlate these biomarkers with outcome

    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.

    Measured: see below

  10. To assess dynamic contrast-enhanced imaging as a potential biomarker.

    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.

    Measured: see below

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2011 (estimated)
  2. Study startOct 2009
  3. Primary completionDec 2015 (estimated)
  4. Study completionDec 2015 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
118 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01274273
Sponsor's protocol ID
DARENCA-1
Status last verified
Aug 2012
First submitted
29 Jun 2010
Last updated
2 Dec 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

    PubMed 37146227

  • Drljevic-Nielsen A, Rasmussen F, Nielsen PS, Stilling C, Thorup K, Mains JR, Madsen HHT, Donskov F. Prognostic value of DCE-CT-derived blood volume and flow compared to core biopsy microvessel density in patients with metastatic renal cell carcinoma. Eur Radiol Exp. 2021 Jul 30;5(1):32. doi: 10.1186/s41747-021-00232-2.

    PubMed 34327591

  • Donskov F, Jensen NV, Smidt-Hansen T, Brondum L, Geertsen P. A randomized phase II trial of interleukin-2 and interferon-alpha plus bevacizumab versus interleukin-2 and interferon-alpha in metastatic renal-cell carcinoma (mRCC): results from the Danish Renal Cancer Group (DaRenCa) study-1. Acta Oncol. 2018 May;57(5):589-594. doi: 10.1080/0284186X.2018.1433324. Epub 2018 Feb 2.

    PubMed 29392960

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Interleukin-2, Interferon Alfa-2b and Bevacizumab in people with Metastatic Renal Cell Carcinoma, run by University of Aarhus at 2 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01274273, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in