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Metastatic Renal Cell CarcinomaPhase 2TORAVANCT00619268

Combination of Temsirolimus and Bevacizumab in Patient With Metastatic Renal Cell Carcinoma

A Phase 2 study testing Temsirolimus, Bevacizumab and Sunitinib in people with Metastatic Renal Cell Carcinoma, run by Centre Leon Berard at 29 sites in France.

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

The TORAVA trial is designed to evaluate the progression-free rate at 48 weeks of a combination of Torisel® and Avastin® given at first-line treatment in patients with metastatic renal cancer. Eligible patients will be randomly assigned, in a 2:1:1 ratio, to either Avastin® + Torisel®, or Sutent® or IFN+Avastin®. 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?
Temsirolimus, Bevacizumab and Sunitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
29 sitesFrance
Study dates
Feb 2008to Feb 2012
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

  • Male or female patients>= 18 years of age;
  • Patients with histological or cytological evidence of metastatic renal cell carcinoma mostly of all type,except for papillary;
  • No prior systemic treatment (chemotherapy, immunotherapy, anti-angiogenic drugs, or treatment under evaluation) for metastatic renal cancer;
  • No brain metastases revealed by MRI or CT-scan within 28 days prior to randomization. Patients with a history of brain metastases treated by surgery +/- radiation therapy can be included if they have normal brain MRI;
  • E.C.O.G performance status =<2;
  • At least one measurable lesion using the RECIST criteria;
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  • Blood tests and renal and liver functions in the normal range with, in the 7 days prior to study entry, blood or serum values as follows:
  • Hemoglobin > 8g/dl; Neutrophil count > 150010exp9/L; Platelets > 10010exp9/L; Serum creatinine < 200µmol/L; Total Bilirubin < 1.5 times upper limit of normal; ALT and AST < 2.5 times upper limit of normal or < 5 ULN for patients with liver metastases, PT or INR < 1.5 times upper limit of normal in the absence of anticoagulant therapy;
  • Absence of proteinuria confirmed by urinary dipstick test
  • Fertile women must use effective means of contraception
  • Mandatory affiliation with a healthy security insurance
  • Signed written informed consent.

Who cannot join

  • Patient with pure papillary renal cell carcinoma
  • Prior systemic treatment for metastatic renal cancer
  • History of other malignancies, other than curatively treated in-situ carcinoma of the cervix or basal cell carcinoma of the skin, or any other curatively treated cancer with no sign of recurrence within 5 years prior to randomization
  • Evidence of brain metastasis by computerized tomographic scan or MRI in the 28 days prior to randomization. Patients with history of brain metastases treated by exclusive brain therapy are not allowed to participate, even if brain MRI is normal
  • Significant cardiovascular disease or uncontrolled hypertension while receiving appropriate medication (>= 160 mm Hg systolic and/or >= 90 mm Hg diastolic)
  • Hepatic affection like chronic advanced hepatitis, liver cirrhosis or chronic hepatitis recently treated or in process of treatment by immunosuppressive agents, hepatitis auto-immune or history of auto-immune disease
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  • Major surgical procedure, open biopsy, or serious non healing wound within 28 days prior to randomization
  • Uncontrolled hypercalcemia while receiving appropriate treatment
  • Uncontrolled hypercholesterolemia or hypertriglyceridemia
  • Patient under anti-vitamin K therapy
  • Patient under strong CYP3A4 inhibitors
  • Patient with severe neuropsychiatric disorder (or comitial crises)
  • Patient included in another clinical trial, except for supportive care trials
  • Pregnant or lactating women (mandatory negative serum or urinary pregnancy test at study entry for all women of childbearing potential)

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

France29 sites

  • Centre Paul Papin

    Angers

  • Centre Hospitalier Universitaire de Besançon

    Besançon

  • Centre Hospitalier Universitaire de Bordeaux - Hôpital St André

    Bordeaux

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre Georges François Leclerc

    Dijon

  • Centre Hospitalier de Versailles

    Le Chesnay

  • Centre Hospitalier Universitaire de Lille - Hôpital Claude Huriez

    Lille

  • Centre Oscar Lambret

    Lille

  • Centre Hospitalier Universitaire DUPUTRYEN

    Limoges

  • Centre Léon Bérard

    Lyon, 69373

  • Centre Hospitalier Universiariare Lyon, Hôpital Lyon Sud

    Lyon

  • Institut Paoli Calmette

    Marseille

  • Centre Val d'Aurelle

    Montpellier

  • Clinique Valdegour-Centre médical Oncogard

    Nîmes

  • Fondation Hôpital Saint Joseph

    Paris

  • Hopital du Val de Grâce

    Paris

  • Hôpital Européen Georges Pompidou

    Paris

  • Centre Hospilier Universitaire de Poitiers

    Poitiers

  • Institut Jean Godinot

    Reims

  • Centre Eugène Marquis

    Rennes

  • Centre René Gauducheau

    Saint-Herblain

  • Institut de Cancérologie de la Loire

    Saint-Priest-en-Jarez

  • Centre Hospitalier Starsbourg

    Strasbourg

  • Hôpital FOCH

    Suresnes

  • Institut Claudius Regaud

    Toulouse

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: Open Label, Randomized, Multicenter Phase II Study of a Combination of Torisel® (Temsirolimus) and Avastin® (Bevacizumab) Versus Sutent® (Sunitinib) and Versus a Combination of Avastin® (Bevacizumab) and Roféron® (Interferon Alpha-2a) in First-line Treatment of Patients With Metastatic Renal Cell Carcinoma.

The TORAVA trial is designed to evaluate the progression-free rate at 48 weeks of a combination of Torisel® and Avastin® given at first-line treatment in patients with metastatic renal cancer.

Eligible patients will be randomly assigned, in a 2:1:1 ratio, to either Avastin® + Torisel®, or Sutent® or IFN+Avastin®.

Read the detailed description

This is a phase II, open label, randomized, parallel group, multicenter study evaluating first-line treatment of patients with metastatic renal cancer using a combination of Torisel® administered intravenously as 25 mg every week and Avastin® administered intravenously as 10 mg/kg every 2 weeks.

Two standard arms with either Sutent® (given orally as 50 mg once daily during 4 weeks, followed by 2 weeks off) or a combination of Avastin® (administered intravenously as 10 mg/kg every 2 weeks) and Interferon (IFN, administered subcutaneously as 9 MU three times a week) will be used to validate the results obtained in the experimental arm (randomization eliminates selection biases), and to assess Sutent® efficacy rate on a more representative population than in Motzer's trial (Motzer NEJM 2007).

The study is not designed to provide head-to-head comparisons between the experimental arm (Avastin® + Torisel®) and the two standard arms (Sutent® and IFN + Avastin®). Randomization will be used as a tool for allocating patients evenly into the 3 treatment arms to ensure proper balance of prognostic factors. If the progression-free rates observed in randomly assigned control patients are inconsistent with historical data, it may be a warning that the results observed for the experimental arm should be viewed with caution. Patients will be randomly assigned to either option in a 2:1:1 ratio (half less patients in the standard arms used only as historical comparators), and stratified according to inclusion center and performance status (ECOG PS 0 vs. 1 vs. 2).

In the absence of severe toxicity, treatment will be continued until documented progression of the disease (RECIST criteria). Toxicity will be evaluated throughout the treatment period and until disappearance or stabilization of the side effect(s). In case of progression, each investigator makes his/her own treatment decisions, provided that all anti-cancer treatments given to the patients within the frame of the study are reported, as well as their results.

Response rates will be assessed between weeks 11-12, 23-24, 35-36, 47-48 in the first year (corresponding to 2 cycles of Sutent®) and every 3 months afterwards until treatment stop, or until patient death or end of clinical data collection.

Being tested
Temsirolimus, Bevacizumab, Sunitinib, Interferon alpha-2a
Keywords
Temsirolimus, Bevacizumab, Metastatic renal cell carcinoma, Non-progression
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.

  • TemsirolimusDrug

    Also called Torisel®

    25 mg once per week administered intravenously

  • BevacizumabDrug

    Also called Avastin®

    10 mg/kg * 1 time /2 weeks administered intravenously

  • SunitinibDrug

    Also called Sutent®

    50 mg administered orally once daily in 6 weeks cycles :4 weeks of treatment followed by 2 weeks off

  • Interferon alpha-2aDrug

    Also called Roféron®

    Administered subcutaneously as 9 MU three times per week

Study groups in NCT00619268
Study groupRoleWhat they receive
AExperimentalNot described
Receives: Drug: Temsirolimus; Drug: Bevacizumab
BActive comparatorNot described
Receives: Drug: Sunitinib
CActive comparatorNot described
Receives: Drug: Bevacizumab; Drug: Interferon alpha-2a

What is being measured

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

  1. progression-free rate

    Measured: at 48 weeks post-treatment

Secondary outcomes (5)

  1. Objective response rate:efficacity

    Measured: Every 12 weeks during 48 weeks

  2. Duration of response

  3. Toxicity

    Measured: at week 2, week 5-6 and after every 5-6 weeks during 48 weeks

  4. Quality of life

    Measured: at inclusion, month 6 and at 1 year

  5. progression-free survival and overall survival

Timeline

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

  1. First posted20 Feb 2008 (estimated)
  2. Study startFeb 2008
  3. Primary completionFeb 2012
  4. Study completionFeb 2012

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
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00619268
Sponsor's protocol ID
TORAVA
Other IDs
ET2007-035
Acronym
TORAVA
Status last verified
Feb 2013
First submitted
8 Feb 2008
Last updated
15 Feb 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):125-34. doi: 10.1056/NEJMoa060655.

    PubMed 17215530

  • Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. doi: 10.1056/NEJMoa065044.

    PubMed 17215529

  • Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007 May 31;356(22):2271-81. doi: 10.1056/NEJMoa066838.

    PubMed 17538086

  • Negrier S, Gravis G, Perol D, Chevreau C, Delva R, Bay JO, Blanc E, Ferlay C, Geoffrois L, Rolland F, Legouffe E, Sevin E, Laguerre B, Escudier B. Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. Lancet Oncol. 2011 Jul;12(7):673-80. doi: 10.1016/S1470-2045(11)70124-3. Epub 2011 Jun 12.

    PubMed 21664867

  • 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

  • Polena H, Creuzet J, Dufies M, Sidibe A, Khalil-Mgharbel A, Salomon A, Deroux A, Quesada JL, Roelants C, Filhol O, Cochet C, Blanc E, Ferlay-Segura C, Borchiellini D, Ferrero JM, Escudier B, Negrier S, Pages G, Vilgrain I. The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma. Br J Cancer. 2018 May;118(9):1179-1188. doi: 10.1038/s41416-018-0054-5. Epub 2018 Mar 22.

    PubMed 29563634

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Temsirolimus, Bevacizumab and Sunitinib in people with Metastatic Renal Cell Carcinoma, run by Centre Leon Berard at 29 sites in France.

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 12 inclusion and 14 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 15 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in France. 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?

progression-free rate (time frame: at 48 weeks post-treatment). 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 NCT00619268, which also lists 6 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 15 Feb 2013.

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