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

February 14, 2013 updated by: Centre Leon Berard

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®.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

160

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

  • France
      • Angers, France
        • Centre Paul Papin
      • Besançon, France
        • CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON
      • Bordeaux, France
        • Institut Bergonie
      • Bordeaux, France
        • Centre Hospitalier Universitaire de Bordeaux - Hôpital St André
      • Caen, France
        • Centre Francois Baclesse
      • Clermont Ferrand, France
        • Centre Jean Perrin
      • Dijon, France
        • Centre Georges François Leclerc
      • Le Chesnay, France
        • Centre Hospitalier De Versailles
      • Lille, France
        • Centre Oscar Lambret
      • Lille, France
        • Centre Hospitalier Universitaire de Lille - Hôpital Claude Huriez
      • Limoges, France
        • Centre Hospitalier Universitaire DUPUTRYEN
      • Lyon, France, 69373
        • Centre Leon Berard
      • Lyon, France
        • Centre Hospitalier Universiariare Lyon, Hôpital Lyon Sud
      • Marseille, France
        • Institut Paoli Calmette
      • Montpellier, France
        • Centre Val d'Aurelle
      • Nîmes, France
        • Clinique Valdegour-Centre médical Oncogard
      • Paris, France
        • Hôpital Européen Georges Pompidou
      • Paris, France
        • Hôpital du Val de Grâce
      • Paris, France
        • Fondation Hôpital Saint Joseph
      • Poitiers, France
        • Centre Hospilier Universitaire de Poitiers
      • Reims, France
        • Institut Jean Godinot
      • Rennes, France
        • Centre Eugene Marquis
      • Saint Herblain, France
        • Centre René Gauducheau
      • Saint Priest en Jarez, France
        • Institut de Cancerologie de La Loire
      • Strasbourg, France
        • Centre Hospitalier Starsbourg
      • Suresnes, France
        • Hopital Foch
      • Toulouse, France
        • Institut Claudius Regaud
      • Vandoeuvre les Nancy, France
        • Centre Alexis Vautrin
      • Villejuif, France, 94805
        • Institut Gustave Roussy

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:

  • 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.

Exclusion Criteria:

  • 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)

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: B
Drug: Sunitinib
50 mg administered orally once daily in 6 weeks cycles :4 weeks of treatment followed by 2 weeks off
Other Names:
  • Sutent®
Experimental: A
Drug: Temsirolimus
25 mg once per week administered intravenously
Other Names:
  • Torisel®
Drug: Bevacizumab
10 mg/kg * 1 time /2 weeks administered intravenously
Other Names:
  • Avastin®
Active Comparator: C
Drug: Bevacizumab
10 mg/kg * 1 time /2 weeks administered intravenously
Other Names:
  • Avastin®
Drug: Interferon alpha-2a
Administered subcutaneously as 9 MU three times per week
Other Names:
  • Roféron®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
progression-free rate
Time Frame: at 48 weeks post-treatment
at 48 weeks post-treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Duration of response
Objective response rate:efficacity
Time Frame: Every 12 weeks during 48 weeks
Every 12 weeks during 48 weeks
Toxicity
Time Frame: at week 2, week 5-6 and after every 5-6 weeks during 48 weeks
at week 2, week 5-6 and after every 5-6 weeks during 48 weeks
Quality of life
Time Frame: at inclusion, month 6 and at 1 year
at inclusion, month 6 and at 1 year
progression-free survival and overall survival

Collaborators and Investigators

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

Sponsor

Centre Leon Berard

Investigators

  • Principal Investigator: Bernard ESCUDIER, MD, Gustave Roussy, Cancer Campus, Grand Paris

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

February 1, 2008

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

February 1, 2012

Study Registration Dates

First Submitted

February 8, 2008

First Submitted That Met QC Criteria

February 8, 2008

First Posted (Estimate)

February 20, 2008

Study Record Updates

Last Update Posted (Estimate)

February 15, 2013

Last Update Submitted That Met QC Criteria

February 14, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TORAVA
  • ET2007-035

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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