ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma

Study Overview
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Brief Summary
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This is a phase II multicentre, uncontrolled trial including patients ≤ 40 years with non-metastatic extremity high-grade osteosarcoma stratified according to P-glicoprotein expression

Detailed Description
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The main objective of the study is to evaluate the impact on event-free survival (EFS) of a multi-drug chemotherapy approach and mifamurtide treatment in patients with non-metastatic osteosarcoma of the extremities according to the expression of ABCB1/P-glycoprotein

Official Title
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ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma - Prospective Study (ISG/OS-2)

Conditions
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Osteosarcoma

Intervention / Treatment
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* Drug: Mifamurtide arm
* Other: 3 drugs arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histology confirmed diagnosis of extremities high grade osteosarcoma Age ≤ 40 years Localized disease or presence of skip metastasis Hepatic, renal and bone marrow normal function LVEF > 50% No previous surgery and/ or chemotheraputic osteosarcoma treatments, No more than 4 weeks interval between histological diagnosis and start of chemotherapy Informed consent to the study participation obtained. Exclusion Criteria: Presence of metastases other than skip metastases Periosteal Osteosarcoma, parostal osteosarcoma, secondary osteosarcoma, Medical contra-indication to the drugs foreseen in the protocol, Subject is pregnant or breast feeding Mental or social conditions that can compromise a correct adherence to the protocol and its procedures

Ages Eligible for Study
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Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mifamurtide arm<br>Chemotherapy for patients who over express ABCB1/P-glycoprotein (methotrexate, cisplatinum, doxorubicine, ifosfamide + mifamurtide) | Drug: Mifamurtide arm<br>* PRE SUGERY TREATMENT: Methotrexate: 12g/m2 (3 cycles) Cisplatinum: 120mg/m2 (3 cycles) Doxorubicin: ADM 75mg/m2 (3 cycles) POST SURGERY TREATMENT for good responder patients with positive P-GLYCOPROTEIN Methotrexate 12g/m2 (10 Cycles) Cisplatinum 120mg/m2; Doxorubicin 90mg/m2 MEPACT 2 mg/m2 twice a week for the first 3 months the weekly for the next 6 months (total lenght treatment 44 weeks) POST SURGERY TREATMENT for poor responder patients with positive P-GLYCOPROTEIN Methotrexate 12g/m2; Cisplatinum 120mg/m2; Doxorubicin 90mg/m2 ifosfamide 15g/m2 MEPACT 2 mg/m2 twice a week for the first 3 months the weekly for the next 6 months (total lenght treatment 44 weeks) All the product are used as commercial formulation<br>* Other names: mifamurtide;|
| Other: 3 drugs arm<br>High grade osteosarcoma treatment for patients who do not over express ABCB1/P-glycoprotein | Other: 3 drugs arm<br>* High grade osteosarcoma who do not over express ABCB1/P-glycoprotein will be treated with a standard 3-drugs regimen PRE-SUGERY TREATMENT: Methotrexate: 12g/m2 (3 cycles) Cisplatinum: 120mg/m2 (3 cycles) Doxorubicin: ADM 75mg/m2 (3 cycles) POST SURGERY TREATMENT: Methotrexate 12g/m2 (10 cycles) Cisplatinum 120mg/m2; Doxorubicin 90mg/m2 Total lenght 34 weeks All the product are used as commercial formulation<br>* Other names: doxorubicine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Events free survival | Onset of any event. An event is the defined as disease recurrence (local or distant), death for disease or any other cause, onset of secondary tumors or the last follow-up examination | After 5 years from the time to first day of chemotherapy for all patients and from the date of surgery for the Pgp overexpression patients stratified according to tumor necrosis (Good Responders and Poor Responders). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time elapsed for the diagnosis to the death for any cause or to the last follow-up examination. | After 5 years from the time to first day of chemotherapy for all patients and from the date of surgery for the Pgp overexpression patients stratified according to tumor necrosis (Good Responders and Poor Responders). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non metastatic extremities high grade osteosarcoma