Combination of Temsirolimus and Bevacizumab in Patient With Metastatic Renal Cell Carcinoma
TORAVA
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.
2 other identifiers
interventional
160
1 country
29
Brief 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®.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2008
Typical duration for phase_2
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2008
CompletedFirst Submitted
Initial submission to the registry
February 8, 2008
CompletedFirst Posted
Study publicly available on registry
February 20, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2012
CompletedFebruary 15, 2013
February 1, 2013
4 years
February 8, 2008
February 14, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
progression-free rate
at 48 weeks post-treatment
Secondary Outcomes (5)
Objective response rate:efficacity
Every 12 weeks during 48 weeks
Duration of response
Toxicity
at week 2, week 5-6 and after every 5-6 weeks during 48 weeks
Quality of life
at inclusion, month 6 and at 1 year
progression-free survival and overall survival
Study Arms (3)
A
EXPERIMENTALB
ACTIVE COMPARATORC
ACTIVE COMPARATORInterventions
50 mg administered orally once daily in 6 weeks cycles :4 weeks of treatment followed by 2 weeks off
Administered subcutaneously as 9 MU three times per week
Eligibility Criteria
You may qualify if:
- 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;
- 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 \> 1500\*10exp9/L; Platelets \> 100\*10exp9/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.
You may not qualify if:
- 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
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (29)
Centre Paul Papin
Angers, France
Centre Hospitalier Universitaire de Besançon
Besançon, France
Centre Hospitalier Universitaire de Bordeaux - Hôpital St André
Bordeaux, France
Institut Bergonié
Bordeaux, France
Centre François Baclesse
Caen, France
Centre Jean Perrin
Clermont-Ferrand, France
Centre Georges François Leclerc
Dijon, France
Centre Hospitalier de Versailles
Le Chesnay, France
Centre Hospitalier Universitaire de Lille - Hôpital Claude Huriez
Lille, France
Centre Oscar Lambret
Lille, France
Centre Hospitalier Universitaire DUPUTRYEN
Limoges, France
Centre Léon Bérard
Lyon, 69373, France
Centre Hospitalier Universiariare Lyon, Hôpital Lyon Sud
Lyon, France
Institut Paoli Calmette
Marseille, France
Centre Val d'Aurelle
Montpellier, France
Clinique Valdegour-Centre médical Oncogard
Nîmes, France
Fondation Hôpital Saint Joseph
Paris, France
Hopital du Val de Grâce
Paris, France
Hôpital Européen Georges Pompidou
Paris, France
Centre Hospilier Universitaire de Poitiers
Poitiers, France
Institut Jean Godinot
Reims, France
Centre Eugène Marquis
Rennes, France
Centre René Gauducheau
Saint-Herblain, France
Institut de Cancérologie de la Loire
Saint-Priest-en-Jarez, France
Centre Hospitalier Starsbourg
Strasbourg, France
Hôpital FOCH
Suresnes, France
Institut Claudius Regaud
Toulouse, France
Centre Alexis Vautrin
Vandœuvre-lès-Nancy, France
Institut Gustave Roussy
Villejuif, 94805, France
Related Publications (6)
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.
PMID: 17215530BACKGROUNDMotzer 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.
PMID: 17215529BACKGROUNDHudes 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.
PMID: 17538086BACKGROUNDNegrier 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.
PMID: 21664867RESULTAldin 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.
PMID: 37146227DERIVEDPolena 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.
PMID: 29563634DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sylvie NEGRIER, MD, PhD
Centre Leon Berard
- PRINCIPAL INVESTIGATOR
Bernard ESCUDIER, MD
Gustave Roussy, Cancer Campus, Grand Paris
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 8, 2008
First Posted
February 20, 2008
Study Start
February 1, 2008
Primary Completion
February 1, 2012
Study Completion
February 1, 2012
Last Updated
February 15, 2013
Record last verified: 2013-02