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

Osteosarcoma Clinical Trial

— ISG/OS-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01459484
• Other study ID #: ISG/OS-2
• Secondary ID: 2011-001659-36
• Status: Completed
• Phase: Phase 2
• Start date: June 23, 2011
• Est. completion date: April 30, 2024

Study information

• Verified date: May 2024
• Source: Italian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteosarcoma

Intervention

Drug:
• Mifamurtide arm
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

Other:
• 3 drugs arm
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

Locations

Country	Name	City	State
Italy	IRCCS Istituto ortopedico Rizzoli	Bologna
Italy	I.R.C.C. - Unit of Medical Oncology	Candiolo	Torino
Italy	A.O. Universitaria Meyer	Firenze
Italy	Istituto Giannina Gaslini	Genova
Italy	FONDAZIONE IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Nazionale Tumori "Fondazione G. Pascale"	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Istituti Fisioterapici Ospitalieri di Roma	Roma
Italy	Ospedale Pediatrico Bambin Gesu'	Roma
Italy	Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology	Torino
Italy	Presidio Sanitario Gradenigo	Torino	TO

Sponsors (1)

Lead Sponsor	Collaborator
Italian Sarcoma Group

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Serra M, Pasello M, Manara MC, Scotlandi K, Ferrari S, Bertoni F, Mercuri M, Alvegard TA, Picci P, Bacci G, Smeland S. May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol. Int J Oncol. 2006 Dec;29(6):1459-68. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).