Adjuvant High-Dose Thiotepa and Stem Cell Rescue Associated With Conventional Chemotherapy in Relapsed Osteosarcoma
Condition: Osteosarcoma
MeSH terms: Osteosarcoma
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Thiotepa
Intervention type(s): Drug
Intervention description(s): Thiotepa 8-12mg/m²/day/injection Total dose for one cure:15-50mg.
Other intervention name(s): N N'N'triethylenethiophosphosphoramide; Tepadina
Intervention MeSH terms: Thiotepa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Conventional chemotherapy; cytapheresis; Peripheral stem cell autograft; Surgical resection; Thiotepa