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

Italian Sarcoma Group225 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

225

Conditions

Osteosarcoma

Interventions

Mifamurtide armDRUG

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

3 drugs armOTHER

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

Eligibility

Sex: ALLMax age: 40 Years

Medical Language ↔ Plain English

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

Locations (11)

I.R.C.C. - Unit of Medical Oncology

Candiolo, Torino, Italy

Presidio Sanitario Gradenigo

Torino, TO, Italy

IRCCS Istituto ortopedico Rizzoli

Bologna, Italy

Outcomes

Primary Outcomes

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

Time frame: 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 Outcomes

Overall Survival

Time elapsed for the diagnosis to the death for any cause or to the last follow-up examination.

Data from ClinicalTrials.gov

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