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Metastatic Renal Cell CarcinomaPhase 2BERATNCT01731158

Sequential Therapy in Metastatic Renal Cell Carinoma

A Phase 2 study testing Avastin in combination with Roferon-A, Afinitor and TKI: Sutent, Nexavar or Votrient in people with Metastatic Renal Cell Carcinoma, run by Central European Society for Anticancer Drug Research at 13 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Sequential therapy with BEvacizumab, RAd001 (everolimus) and Tyrosinekinase inhibitors (TKI) in 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?
Avastin in combination with Roferon-A, Afinitor and TKI: Sutent, Nexavar or Votrient
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
13 sitesGermany
Study dates
Oct 2012to Sep 2016
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 Informed Consent
  • Documented progressive disease prior to study inclusion.
  • Adult males and females: ≥ 18 years of age.
  • Metastatic or locally advanced RCC, not amendable to surgery with curative intention.
  • ECOG performance status 0-1.
  • Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated. Patients with bone lesions as the only measurable lesion are eligible, provided that lesions consist of soft tissue, which is assessed via CT or MRI.
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  • Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery 2 weeks) prior to start of treatment and patient recovered from toxic effects.
  • Modified MSKCC risk (according to Heng): good or intermediate.
  • White blood cell count (WBC) ≥ 4x10*9/L with neutrophils ≥ 1.5 x 10*9/L, platelet count ≥ 100x10*9/L, hemoglobin ≥ 9 g/dL.
  • Total bilirubin ≤ 2 x upper limit of normal.
  • AST and ALT ≤ 2.5 x upper limit of normal, or ≤ 5 x upper limit of normal in case of liver metastases.
  • Serum creatinine ≤ 2 x upper limit of normal or calculated creatinine clearance >30 ml/min.
  • International Normalized Ratio (INR) ≤1.5 except for patients on stable anticoagulant therapy. Activated partial thromboplastin time (aPTT) ≤1.5 times upper limit of normal (ULN) or greater than the lower limit of the therapeutic range. Note: The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the treatment start.
  • Adequate cardiac function (left ventricular ejection fraction ≥50% as assessed by ECHO)

Who cannot join

  • Any investigational drug within the 30 days before inclusion.
  • Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments or their excipients.
  • Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
  • Men or women of child-bearing potential who are sexually active and unwilling to use a highly effective method of contraception (Pearl index < 1%) during the trial. Oral contraceptives are acceptable if a barrier method is applied in conjunction.
  • Clinically symptomatic brain or meningeal metastasis (known or suspected), unless completion of local therapy for at least 3 months with discontinuation of steroids prior to start of treatment.
  • Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers, digoxin or digitoxin).
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  • History of any of the following cardiac events within the past 6 months:
  • myocardial infarction (including severe/unstable angina),
  • coronary/peripheral artery bypass graft,
  • congestive heart failure (CHF) (NYHA Class III, or IV),
  • cerebrovascular accident,
  • transient ischemic attack,
  • pulmonary embolism, abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess
  • Hemorrhage ≥ grade 3 or clinically significant hemoptysis within the past 4 weeks
  • Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥ 3 anti-hypertensive drugs).
  • History of relevant pulmonary hypertension or interstitial lung disease or severely impaired lung function.
  • Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea.
  • Previous malignancy (other than renal cell cancer) in the last 3 years, except basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a prostate carcinoma or superficial bladder tumor [Ta, Tis and T1].
  • History of organ allograft.
  • Significant disease which, in the investigator's opinion would exclude the patient from the study.
  • Medication that is known to interfere with any of the agents applied in the trial.
  • Patients with a serious non-healing wound, ulcer or bone fracture.
  • Patients with a history of seizure(s) not controlled with standard medical therapy.
  • Patients receiving chronic systemic treatment with corticosteroids (dose of > 20 mg/day methylprednisone equivalent) or another immune-suppressive agent. Inhaled and topical steroids are acceptable.
  • Legal incapacity or limited legal capacity.
  • Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
  • Significant vascular disease (e.g. aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease.
  • Evidence or history of recurrent thromboembolism (>1 episode of deep venous thrombosis/peripheral embolism ≥ CTCAE Grade 3) during the past 2 years, bleeding diathesis or coagulopathy.
  • Poorly controlled diabetes as defined by fasting serum glucose > 2.0 x ULN.
  • Active (acute or chronic) or uncontrolled infection of bacterial, mycotic or viral genesis.
  • Liver disease such as chronic active hepatitis or chronic persistent hepatitis.
  • Patients with a known history of HIV seropositivity.
  • QT prolongation (QTc > 450 msec).

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Germany13 sites

  • Charité Berlin

    Berlin

  • University Hospital Bonn

    Bonn

  • University Hospital Dresden

    Dresden

  • University Hospital Düsseldorf

    Düsseldorf

  • Waldkrankenhaus St. Marien

    Erlangen

  • University Hospital Essen

    Essen

  • University Hospital Frankfurt

    Frankfurt

  • University Hospital Freiburg

    Freiburg im Breisgau

  • University Hospital Göttingen

    Göttingen

  • Oncological Practice Hannover

    Hanover

  • University Hospital Hannover

    Hanover

  • University Hospital Magdeburg

    Magdeburg

  • University Hospital Tübingen

    Tübingen

Other trials in Germany

About this study

Official title: A Prospective, Open-label, Multicenter, Randomized Phase II Trial: Sequential Therapy With BEvacizumab, RAd001 (Everolimus) and Tyrosinekinase Inhibitors (TKI) in Metastatic Renal Cell Carcinoma (mRCC) (BERAT Study)

Sequential therapy with BEvacizumab, RAd001 (everolimus) and Tyrosinekinase inhibitors (TKI) in metastatic renal cell carcinoma (mRCC)

Read the detailed description

This will be a prospective, open label, randomized multicenter phase-II study to evaluate progression free survival (PFS) in 2nd line treatment in patients with locally advanced or metastatic clear-cell renal cell cancer (cc-RCC) receiving everolimus (arm A) in comparison to a tyrosine-kinase inhibitor (TKI) (arm B). Following 2nd line treatment, patients will be switched to a TKI in arm A and everolimus in arm B. All patients will receive bevacizumab as standardized first-line treatment.

Another key element of the study is the analysis of predictive biomarkers, which will be performed in serum and tumor tissue, respectively. Serum samples will be collected at prespecified timepoints throughout the study and analysed by SELDI-TOF-MS and DIGE. Candidate proteins are thought to predict therapeutic outcome and candidates are subject for target validation by Western Blot or ELISA. In addition, formalin-fixed paraffin-embedded (FFPE) tumor tissue will be collected prospectively and analysed for micro RNA (miRNA). Candidate miRNAs that predict therapeutic outcome will be validated by quantitative RT-PCR. Furthermore, circulating tumor cells (CTCs) will be generated from blood drawings during routine visits. The primary objective is to correlate the marker profile defined from the FFPE tissue with the profile obtained from CTCs in order to validate expression based markers ant their change during different treatment lines.

Being tested
Avastin in combination with Roferon-A, Afinitor, TKI: Sutent, Nexavar or Votrient
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.

  • Avastin in combination with Roferon-ADrug

    Also called Bevacizumab in combination with Interfereon-alfa

  • AfinitorDrug

    Also called Everolimus

  • TKI: Sutent, Nexavar or VotrientDrug

    Also called Sunitinib, Sorafenib or Pazopanib

    TKI

Study groups in NCT01731158
Study groupRoleWhat they receive
arm AOthersequential therapy with approved drugs Avastin in combination with Roferon-A (first-line), Afinitor (second-line) and a TKI (Sutent, Nexavar or Votrient) (third-line)
Receives: Drug: Avastin in combination with Roferon-A; Drug: Afinitor; Drug: TKI: Sutent, Nexavar or Votrient
arm BOthersequential therapy with approved drugs Avastin in combination with Roferon-A (first-line), a TKI (Sutent, Nexavar or Votrient) (second-line) and Afinitor (third-line)
Receives: Drug: Avastin in combination with Roferon-A; Drug: Afinitor; Drug: TKI: Sutent, Nexavar or Votrient

What is being measured

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

  1. PFS rate of 2nd line treatment at 6 months after randomisation

    PFS rate

    Measured: 6 months after randomisation

Secondary outcomes (6)

  1. PFS for 2nd line treatment

    PFS

    Measured: after completion of second-line treatment (expected median treatment 1st and 2nd line: 16 months)

  2. PFS for each treatment given

    PFS

    Measured: after completion of each treatment line (expected median treatment duration 1st line: 11 months, 2nd line: 5 months, 3rd line: 6 months)

  3. Overall Survival

    OS

    Measured: after death of patient

  4. number and severity (CTCAE 4.0) adverse events

    AE

    Measured: continuously throughout trial

  5. changes in quality of life throughout the Trial using FKSI questionnaires

    quality of life

    Measured: continuously throughout trial (baseline, week 5, week 11, every 12 weeks, end of treatment for all treatment lines via FKSI-10 questionnaire)

  6. ORR for each treatment given

    ORR

    Measured: after completion of each treatment line (expected median treatment duration 1st line: 11 months, 2nd line: 5 months, 3rd line: 6 months)

Timeline

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

  1. First posted21 Nov 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionSep 2016
  4. Study completionSep 2016

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
Crossover
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01731158
Sponsor's protocol ID
C-II-008
Other IDs
2011-005939-78
Acronym
BERAT
Status last verified
Feb 2019
First submitted
28 Sep 2012
Last updated
6 Feb 2019
Results posted
No

Publications

  • Nel I, Gauler TC, Bublitz K, Lazaridis L, Goergens A, Giebel B, Schuler M, Hoffmann AC. Circulating Tumor Cell Composition in Renal Cell Carcinoma. PLoS One. 2016 Apr 21;11(4):e0153018. doi: 10.1371/journal.pone.0153018. eCollection 2016.

    PubMed 27101285

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avastin in combination with Roferon-A, Afinitor and TKI: Sutent, Nexavar or Votrient in people with Metastatic Renal Cell Carcinoma, run by Central European Society for Anticancer Drug Research at 13 sites in Germany.

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 14 inclusion and 33 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: finished, as of the sponsor's last update on 6 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

PFS rate of 2nd line treatment at 6 months after randomisation (time frame: 6 months after randomisation). 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 NCT01731158, which also lists 1 linked publication.

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 6 Feb 2019; AzTrials last refreshed its copy on 6 Nov 2026.

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