Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	Other	TORAVA ET2007-035, NCT00619268

Trial Description

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®.

Further Study Information

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 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)

Trial Contact Information

Trial Lead Organizations/Sponsors

Centre Leon Berard

Sylvie Negrier

Principal Investigator

Bernard Escudier

Principal Investigator

David PEROL, MD		Ph: +33 478 78 28 79
		Email: perold@lyon.fnclcc.fr

Ellen BLANC
		Email: blanc@lyon.fnclcc.fr

France
	Angers
	Centre Paul Papin
		Remy DELVA, MD
			Email: r.delva@unimedia.fr
		Remy Delva	Principal Investigator
		Patrick Soulie	Sub-Investigator
		Olivier CAPITAIN, MD	Sub-Investigator
		Sophie Abadie-Lacourtoisie	Sub-Investigator
	Bordeaux
	Hopital Saint Andre
		Alain RAVAUD, MD
			Email: alain.ravaud@chu-bordeaux.fr
		Alain Ravaud	Principal Investigator
	Caen
	Centre Regional Francois Baclesse
		Emmanuel SEVIN, MD
			Email: e.sevin@baclesse.fr
		Emmanuel Sevin	Principal Investigator
	Clermont Ferrand
	Centre Jean Perrin
		Jacques-Olivier BAY, MD, PhD
			Email: olivier.BAY@cjp.fr
		Jacques-Olivier Bay	Principal Investigator
	Dijon
	Centre de Lutte Contre le Cancer Georges-Francois Leclerc
		Sylvie ZANETTA, MD
			Email: szanetta@dijon.fnclcc.fr
		Sylvie ZANETTA, MD	Principal Investigator
		Pierre Fargeot	Sub-Investigator
	Lyon
	Centre Leon Berard
		Sylvie NEGRIER, MD, PhD	Ph: +33 478 78 27 51
			Email: negrier@lyon.fnclcc.fr
		Sylvie Negrier	Principal Investigator
		Aude Flechon	Sub-Investigator
		Eve-Marie NEIDHARDT, MD	Sub-Investigator
	Marseille
	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
		Gwenaëlle GRAVIS, MD
			Email: gravisg@marseille.fnclcc.fr
		Gwenaelle Gravis	Principal Investigator
		Sophie BAGATTINI, MD	Sub-Investigator
		Anthony GONCALVES, MD	Sub-Investigator
	Nîmes
	Clinique De Valdegour
		Eric LEGOUFFE, MD
			Email: legouffe.oncogard@orange.fr
		Eric Legouffe	Principal Investigator
	Paris
	Hopital Europeen Georges Pompidou
		Stéphane OUDARD, MD, PhD
			Email: Stephane.OUDARD@hop.egp.ap-hop-paris.fr
		Stephane Oudard	Principal Investigator
	Hopital Saint Joseph
		Gaël DEPLANQUE, MD
			Email: gdeplanque@hopital-saint-joseph.org
		Sophie Barthier	Sub-Investigator
		Gael Deplanque	Principal Investigator
		Martine GROSS-GOUPIL, MD	Sub-Investigator
		Nadia DJABALI-LEVASSEUR, MD	Sub-Investigator
		Michel GATINEAU, MD	Sub-Investigator
	Reims
	Institut Jean Godinot
		Jean-Christophe EYMARD, MD
		Jean-Christophe Eymard	Principal Investigator
	Rennes
	Centre Eugene Marquis
		Brigitte LAGUERRE, MD
			Email: b.laguerre@rennes.fnclcc.fr
		Brigitte Laguerre	Principal Investigator
	Saint Herblain
	Centre Regional Rene Gauducheau
		Frédéric ROLLAND, MD
			Email: f-rolland@nantes.fnclcc.fr
		Frederic Rolland	Principal Investigator
		Emmanuelle Bompas	Sub-Investigator
	Saint Priest en Jarez
	Institut de Cancerologie de la Loire
		Aline GUILLOT, MD
			Email: aline.guillot@icloire.fr
		Aline GUILLOT, MD	Principal Investigator
		Olivier Collard	Sub-Investigator
	Toulouse
	Institut Claudius Regaud
		Christine CHEVREAU, MD
			Email: chevreau.christine@claudiusregaud.fr
		Christine Chevreau-Dalbianco	Principal Investigator
	Vandoeuvre les Nancy
	Centre Alexis Vautrin
		Lionnel GEOFFROIS, MD
			Email: l.geoffrois@nancy.fnclcc.fr
		Lionnel Geoffrois	Principal Investigator
	Villejuif
	Institut Gustave Roussy
		Bernard ESCUDIER, MD	Ph: +33 142 11 54 10
			Email: bernard.escudier@igr.fr
		Bernard Escudier	Principal Investigator
		Marine GROSS-GOUPIL, MD	Sub-Investigator
		Christophe MASSARD, MD	Sub-Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00619268
Information obtained from ClinicalTrials.gov on March 18, 2009