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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT00619268
First received: February 8, 2008
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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®.


Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Drug: Temsirolimus
Drug: Bevacizumab
Drug: Sunitinib
Drug: Interferon alpha-2a
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • progression-free rate [ Time Frame: at 48 weeks post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate:efficacity [ Time Frame: Every 12 weeks during 48 weeks ] [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: at week 2, week 5-6 and after every 5-6 weeks during 48 weeks ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: at inclusion, month 6 and at 1 year ] [ Designated as safety issue: No ]
  • progression-free survival and overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: February 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Temsirolimus
25 mg once per week administered intravenously
Other Name: Torisel®
Drug: Bevacizumab
10 mg/kg * 1 time /2 weeks administered intravenously
Other Name: Avastin®
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 Name: Sutent®
Active Comparator: C Drug: Bevacizumab
10 mg/kg * 1 time /2 weeks administered intravenously
Other Name: Avastin®
Drug: Interferon alpha-2a
Administered subcutaneously as 9 MU three times per week
Other Name: Roféron®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619268

Locations
France
Centre Paul Papin
Angers, France
Centre Hospitalier Universitaire de Besançon
Besançon, France
Institut Bergonié
Bordeaux, France
Centre Hospitalier Universitaire de Bordeaux - Hôpital St André
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 Oscar Lambret
Lille, France
Centre Hospitalier Universitaire de Lille - Hôpital Claude Huriez
Lille, France
Centre Hospitalier Universitaire DUPUTRYEN
Limoges, France
Centre Léon Bérard
Lyon, France, 69373
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
Vandoeuvre les Nancy, France
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Centre Leon Berard
Investigators
Principal Investigator: Sylvie NEGRIER, MD, PhD Centre Leon Berard
Principal Investigator: Bernard ESCUDIER, MD Gustave Roussy, Cancer Campus, Grand Paris
  More Information

Additional Information:
Publications:
Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT00619268     History of Changes
Other Study ID Numbers: TORAVA, ET2007-035
Study First Received: February 8, 2008
Last Updated: February 14, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:
Temsirolimus
Bevacizumab
Metastatic renal cell carcinoma
Non-progression

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferon-alpha
Interferons
Sirolimus
Everolimus
Bevacizumab
Sunitinib
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014