Adjuvant High-Dose Thiotepa and Stem Cell Rescue Associated With Conventional Chemotherapy in Relapsed Osteosarcoma (OSII-TTP)

This study is currently recruiting participants.

Verified December 2012 by Centre Leon Berard

Sponsor:

Collaborators:

IHOP-HCL

Hôpital Armand Trousseau

Nantes University Hospital

Institut Curie

CHU - HOPITAL DES ENFANTS BORDEAUX

Central Hospital, Nancy, France

University Hospital, Toulouse

Centre Oscar Lambret

Institut Gustave Roussy

HOPITAL DE HAUTEPIERRE

Centre Georges Francois Leclerc

Centre Henri Becquerel

Institut de Cancérologie de la Loire

University Hospital, Grenoble

Information provided by (Responsible Party):

Centre Leon Berard

ClinicalTrials.gov Identifier:

NCT00978471

First received: September 16, 2009

Last updated: December 17, 2012

Last verified: December 2012

History of Changes

Purpose

Approximately 150 new cases of osteosarcoma are reported each year in France, of which 15 to 20% are metastatic.

Further to the initial standard care, about 45% of the patients relapse within a median duration of 20 months.

Result of the OS94 study results and of the investigation performed within the CRLCC, indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE.

According to several studies, the 5-year overall survival rate of patients in first relapse is 23-28%,with a median post relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year.

At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE.

Thiotepa is known for its antitumor effect in numerous malignant tumors. In 2007, a study from our institution reported that about 35% of all osteosarcoma relapses are treated with a high-dose thiotepa while the efficacy and tolerance of this therapeutic strategy have never been assessed.

These results highlight the need to the evaluate the efficacy and tolerance of this high-dose of thiotepa within a clinical trial and its inclusion in the standard care of the osteosarcoma at relapse.

Condition	Intervention	Phase
Osteosarcoma	Drug: Thiotepa	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:	Efficacy and Tolerance Adjuvant High-Dose Thiotepa With Peripheral Stem Cell Rescue Associated With Conventional Chemotherapy in Children and Adults With Relapsed Osteosarcoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Thiotepa

U.S. FDA Resources

Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:

Estimate the overall survival rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Estimate overall survival after relapse diagnosis [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Estimate the survival free progression after randomization [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Evaluate the tolerance profile of experimental treatment (hematologic toxicity) [ Time Frame: every 3 weeks ] [ Designated as safety issue: No ]
Estimate the rate of tumor response to treatment as assessed by conventional CT-scan [ Time Frame: at inclusion, day 14-day 21 after the 2nd chemotherapy cycle, before randomization, day 14-day 21 after the 4th chemotherapy cycle, after thiotepa cure and 8 weeks after the end of treatment ] [ Designated as safety issue: No ]
Estimate histological response to treatment on surgical tumor samples [ Time Frame: If surgery is applicable, a few weeks after thiotepa cure (12 to 17 weeks after inclusion) ] [ Designated as safety issue: No ]
Study of biological and genomic properties and analysis of angiogenic markers correlated with relapse (optional) [ Time Frame: At inclusion,at surgery , and at the end of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	66
Study Start Date:	July 2009
Estimated Study Completion Date:	September 2016
Estimated Primary Completion Date:	September 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: experimental arm thiotepa 4 courses of conventional chemotherapy followed by high-dose Thiotepa with peripheral stem cell rescue. Surgical resection of all tumor masses will be performed as soon as possible.	Drug: Thiotepa Thiotepa 8-12mg/m²/day/injection Total dose for one cure:15-50mg. Other Names: N N'N'triethylenethiophosphosphoramide Tepadina
Reference arm 4 courses of conventional chemotherapy. Surgical resection of all tumor masses will be performed as soon as possible.	Drug: Thiotepa Thiotepa 8-12mg/m²/day/injection Total dose for one cure:15-50mg. Other Names: N N'N'triethylenethiophosphosphoramide Tepadina

Detailed Description:

Despite the absence of tumor registry, approximately 150 new cases of osteosarcoma are reported each year in France (100 cases per year in children and 50 cases in adults), of which 15 to 20% are metastatic. The standardized impact rate in the world population is estimated at 3 per million inhabitants per year.

Further to the initial standard care, about 45% of the patients relapse within a median interval of 20 months (range 3 months - 10 years).

Results of the OS94 study and of the investigation performed within the CRLCC indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE.

Results of the five major published series indicate that the 5-year overall survival rate of patients in first relapse is between 23 and 28%, with a median post-relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year.

At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE.

Some recommendations have been given in the OS94 protocol, but they are generally not followed or they are implemented in a heterogeneous manner.

Thiotepa (N N' N'' triethylenethiophosphoramide), an alkylating agent of the chemical family of ethylene-imines, is known for its antitumor effect in a number of malignant tumors.

Its efficacy in osteosarcoma has been reported in the literature. A retrospective study of the SFCE (French Society for Childhood Cancer, results not yet published) in 45 patients presenting with refractory osteosarcoma or relapse has shown a radiological reaction rate of 30%.

Moreover, a preliminary investigation performed by the CLB in 2007 within the framework of the SFCE study explored all relapse cases diagnosed between the beginning of 2004 and the end of 2006. Results showed that about 35% of the patients with osteosarcoma relapses are treated with high-dose thiotepa while the efficacy and tolerance of this therapeutic strategy have never been assessed.

Altogether, these results led the SFCE osteosarcoma group to propose the evaluation of the efficacy and tolerance of this high-dose thiotepa chemotherapy within a clinical trial and to include the drug in the standard care of osteosarcoma in relapse.

Eligibility

Ages Eligible for Study:	1 Year to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age > 1 year and < 50 years
First osteosarcoma relapse, either local or metastatic, or second relapse after exclusive surgery NB: Whenever possible, only patients with histological evidence of relapse will be included.
Indication for chemotherapy confirmed by a multidisciplinary committee.
Surgical resection of all tumor sites must be possible, either as first-line therapy or after chemotherapy.
Lansky score ≥ 60%, or ECOG Performance Status ≤ 2
≥ 21-day interval after first-line chemotherapy
Blood tests, renal and liver functions within the normal range for age with, in particular, 7 days prior to study entry, blood or serum values as follows:
blood: neutrophil count > 1 G/L; platelets >100 G/L
renal: serum creatinine ≤ 1.5 x ULN depending on age; patients with serum creatinine values > 1.5 x ULN are eligible if creatinine clearance is > 70 mL/min/1.73 m²
liver: total bilirubin < 2 x ULN; ASAT and ALAT ≤ 5 x ULN
cardiac: isotopic or echographic Left Ventricular Ejection Fraction > 50 %.
Signed written informed consent; for children, signed consent from the patient (depending on age) and from the parents or legal representative is mandatory
Documented negative serum βHCG for female patients of childbearing age
Affiliation with health insurance.

Exclusion Criteria:

Patients with multiple relapses for whom surgical resection seems impossible, even after chemotherapy.
Patients already treated with high-dose chemotherapy regimens
Patients with a contra-indication to the treatment proposed
Patients not eligible for leukapheresis
Two-year follow-up impossible due to social, family, geographic or psychological reasons
Patient included in another protocol of clinical research
Pregnant or lactating women.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00978471

Contacts

Contact: Perrine MAREC-BERARD, MD	04 78 78 26 42	perrine.marec-berard@lyon.unicancer.fr
Contact: Anne LEFRANC	04.78.78.59.46	anne.lefranc@lyon.unicancer.fr

Locations

France
CHU - Hôpital Saint-Jacques et Jean Minjoz	Recruiting
Besancon, France, 25000
Contact: LAITHIER Veronique, MD 03 81 66 81 66 vlaithier@chu-besancon.fr
Principal Investigator: LAITHIER Veronique, MD
Chu - Hopital Des Enfants Bordeaux	Suspended
Bordeaux, France, 33000
Chu Grenoble	Recruiting
Grenoble, France, 38045
Contact: Dominique Plantaz, MD 04 76 76 54 69 DPlantaz@chu-grenoble.fr
Sub-Investigator: Corinne Armari-Alla, MD
Sub-Investigator: Anne Pagnier, MD
Sub-Investigator: Laure Cotta, MD
Sub-Investigator: PLANTAZ Dominique, MD
Centre Oscar Lambret	Recruiting
Lille, France, 59000
Contact: WATELLE Fabienne, MD f-watelle@o-lambret.fr
Principal Investigator: WATELLE Fabienne, MD
Sub-Investigator: PENEL Nicolas, MD
Principal Investigator: LERVAT Cyril, MD
Centre Léon Bérard - Institut d'Hémato-Oncologie Pediatrique	Recruiting
LYON Cedex 08, France, 69373
Contact: Perrine MAREC-BERARD, MD 04 78 78 26 42 perrine.marec-berard@lyon.unicancer.fr
Contact: Anne LEFRANC 04.78.78.59.46 anne.lefranc@lyon.unicancer.fr
Sub-Investigator: Cécile Conter, MD
Sub-Investigator: Pierre Biron, MD
Sub-Investigator: Jean-yves Blay, MD
Sub-Investigator: Isabelle Ray-Coquard, MD
Principal Investigator: MAREC-BERARD Perrine, MD
Sub-Investigator: DOMMANGE-ROMERO Florence, MD
Sub-Investigator: FRAPPAZ Didier, MD
Institut Paoli Calmettes	Suspended
Marseille, France, 13273
Hôpital des Enfants de la Timone	Recruiting
Marseille, France, 13385
Contact: GENTET Jean-Claude, Pr 0491386821 jcgentet@ap-hm.fr
Principal Investigator: GENTET Jean-Claude, MD
Chu Nantes - Hopital Meres Et Enfants	Recruiting
Nantes, France, 44093
Contact: Nadège Corradini, MD 02 40 08 78 25 ncorradini@chu-nantes.fr
Principal Investigator: CORRADINI Nadège, MD
Institut Curie	Recruiting
Paris, France, 75248
Contact: Hélène Pacquement, MD 0144324601 helenepacquement@curie.net
Sub-Investigator: Daniel Orbach, MD
Sub-Investigator: François Doz, MD
Sub-Investigator: Gudrun Schleiemacher, MD
Sub-Investigator: Jean Michon, MD
Principal Investigator: PACQUEMENT Hélène, MD
Hopital D'Enfants Armand Trousseau	Recruiting
Paris, France, 75571
Contact: Marie-Dominique Tabone, MD 01 44 73 69 06 marie-dominique.tabone@trs.ap-hop-paris.fr
Sub-Investigator: Guy Leverger, MD
Sub-Investigator: Perle Maliszewick, MD
Sub-Investigator: Anne Auvrignon, MD
Sub-Investigator: Judith LandmanParker, MD
Sub-Investigator: Arnaud Petit, MD
Principal Investigator: TABONE Marie-Dominique, MD
CHU RENNES - Hôpital Sud	Recruiting
Rennes, France, 35023
Contact: GANDEMER Virginie, MD 0299265835 virginie.gandemer@chu-rennes.fr
Principal Investigator: GANDEMER Virginie, MD
Sub-Investigator: TAQUE Sophie, MD
Sub-Investigator: CHAPPE Céline, MD
Sub-Investigator: TOUTAIN Fabienne, MD
Sub-Investigator: EDAN Christine, MD
Sub-Investigator: BAYART Sophie, MD
CHU de SAINT-ETIENNE, Hôpital Nord	Recruiting
Saint Priest en Jarez, France, 42270
Contact: Claire Berger, MD 04 77 91 70 00 claire.berger@chu-st-etienne.fr
Sub-Investigator: Jean Louis Stephan, MD
Sub-Investigator: Sandrine Thouvenin, MD
Principal Investigator: BERGER Claire, MD
Centre René Gauducheau	Recruiting
Saint-herblain, France, 44805
Contact: BOMPAS Emmanuelle, MD 0240679939 e-bompas@nantes.fnclcc.fr
Principal Investigator: BOMPAS Emmanuelle, MD
Institut de Cancerologie de la Loire	Suspended
Saint-Priest-en -Jarez, France, 42270
Hopital de Hautepierre	Suspended
Strasbourg, France, 67098
Chu Toulouse - Hopital D'Enfants	Suspended
Toulouse, France, 31059
Chu Nancy - Hopital D'Enfants	Recruiting
Vandoeuvre Les Nancy, France, 54511
Contact: Claudine Schmitt, MD 03831530 c.schmitt@chu-nancy.fr
Principal Investigator: SCHMITT Claudine, MD
Sub-Investigator: CHASTAGNER Pascal, MD
Sub-Investigator: FOUYSSAC Fanny, MD
Sub-Investigator: PHULPIN-WEIBEL Aurelie, MD
Institut Gustave Roussy	Recruiting
Villejuif, France, 95805
Contact: Laurence Brugières, MD 0142114180 brugières@igr.fr
Sub-Investigator: Axel Le Cesne, MD
Principal Investigator: BRUGIERES Laurence, MD

Sponsors and Collaborators

Centre Leon Berard

IHOP-HCL

Hôpital Armand Trousseau

Nantes University Hospital

Institut Curie

CHU - HOPITAL DES ENFANTS BORDEAUX

Central Hospital, Nancy, France

University Hospital, Toulouse

Centre Oscar Lambret

Institut Gustave Roussy

HOPITAL DE HAUTEPIERRE

Centre Georges Francois Leclerc

Centre Henri Becquerel

Institut de Cancérologie de la Loire

University Hospital, Grenoble

Investigators

Principal Investigator:

Perrine MAREC-BÉRARD, Dr

Institut d'Hématologie et d'Oncologie Pédiatrique (IHOP) - CLB

More Information

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Responsible Party:	Centre Leon Berard
ClinicalTrials.gov Identifier:	NCT00978471 History of Changes
Other Study ID Numbers:	OSII-TTP, 2009-009899-12
Study First Received:	September 16, 2009
Last Updated:	December 17, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:

Conventional chemotherapy
cytapheresis
Peripheral stem cell autograft
Surgical resection
Thiotepa

Additional relevant MeSH terms:

Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Thiotepa
Antineoplastic Agents, Alkylating

Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013

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