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

Osteosarcoma Clinical Trial

— OSII-TTP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00978471
• Other study ID #: OSII-TTP
• Secondary ID: 2009-009899-12
• Status: Completed
• Phase: Phase 2
• Start date: July 2009
• Est. completion date: October 29, 2018

Study information

• Verified date: August 2018
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: October 29, 2018
• Est. primary completion date: October 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 50 Years

Eligibility

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 ßHCG 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.

Related Conditions & MeSH terms

• Osteosarcoma

Intervention

Drug:
• Thiotepa
Thiotepa 8-12mg/m²/day/injection Total dose for one cure:15-50mg.

Locations

Country	Name	City	State
France	CHU Besançon- Hôpital Jean Minjoz	Besancon
France	Chu - Hopital Des Enfants Bordeaux	Bordeaux
France	CHU Dijon Le Bocage, Hôpital d'Enfants	Dijon
France	Chu Grenoble	Grenoble
France	Centre Oscar Lambret	Lille
France	Centre Léon Bérard - Institut d'Hémato-Oncologie Pediatrique	LYON Cedex 08
France	Hôpital des Enfants de la Timone	Marseille
France	Institut Paoli Calmettes	Marseille
France	Chu Nantes - Hopital Meres Et Enfants	Nantes
France	Centre Antoine Lacassagne	Nice
France	CHU Nice, Hôpital L'Archet 2	Nice
France	Hopital D'Enfants Armand Trousseau	Paris
France	Institut Curie	Paris
France	CHU Poitiers, site de la Milétrie	Poitiers
France	CHU RENNES - Hôpital Sud	Rennes
France	CHU de SAINT-ETIENNE, Hôpital Nord	Saint Priest en Jarez
France	Chu La Reunion	Saint-denis
France	Institut de Cancérologie de l'Ouest - René Gauducheau	Saint-herblain
France	Institut Lucien Neurwith	Saint-Priest-en -Jarez
France	Hopital de Hautepierre	Strasbourg
France	Chu Toulouse - Hopital D'Enfants	Toulouse
France	Chu Nancy - Hopital D'Enfants	Vandoeuvre Les Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Centre Leon Berard

Country where clinical trial is conducted

France, 

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* Note: There are 46 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimate the overall survival rate		24 months
Secondary	Estimate overall survival after relapse diagnosis		24 months
Secondary	Estimate the survival free progression after randomization		24 months
Secondary	Evaluate the tolerance profile of experimental treatment (hematologic toxicity)		every 3 weeks
Secondary	Estimate the rate of tumor response to treatment as assessed by conventional CT-scan		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
Secondary	Estimate histological response to treatment on surgical tumor samples		If surgery is applicable, a few weeks after thiotepa cure (12 to 17 weeks after inclusion)
Secondary	Study of biological and genomic properties and analysis of angiogenic markers correlated with relapse (optional)		At inclusion,at surgery , and at the end of treatment