ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma
ISG/OS-2
2 other identifiers
interventional
225
1 country
11
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2011
Longer than P75 for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 23, 2011
CompletedFirst Submitted
Initial submission to the registry
October 19, 2011
CompletedFirst Posted
Study publicly available on registry
October 25, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2024
CompletedMay 20, 2024
May 1, 2024
12.9 years
October 19, 2011
May 17, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
Overall Survival
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).
Study Arms (2)
Mifamurtide arm
EXPERIMENTALChemotherapy for patients who over express ABCB1/P-glycoprotein (methotrexate, cisplatinum, doxorubicine, ifosfamide + mifamurtide)
3 drugs arm
OTHERHigh grade osteosarcoma treatment for patients who do not over express ABCB1/P-glycoprotein
Interventions
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
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 Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
I.R.C.C. - Unit of Medical Oncology
Candiolo, Torino, 10060, Italy
Presidio Sanitario Gradenigo
Torino, TO, 10153, Italy
IRCCS Istituto ortopedico Rizzoli
Bologna, 40136, Italy
A.O. Universitaria Meyer
Florence, 50139, Italy
Istituto Giannina Gaslini
Genova, Italy
FONDAZIONE IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Nazionale Tumori "Fondazione G. Pascale"
Napoli, 80131, Italy
Azienda Ospedaliera di Padova
Padua, Italy
Istituti Fisioterapici Ospitalieri di Roma
Roma, Italy
Ospedale Pediatrico Bambin Gesu'
Roma, Italy
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
Torino, 10126, Italy
Related Publications (4)
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.
PMID: 17088985BACKGROUNDPalmerini E, Meazza C, Tamburini A, Marquez-Vega C, Bisogno G, Fagioli F, Ferraresi V, Milano GM, Coccoli L, Rubio-San-Simon A, Gallego O, Llinares Riestra ME, Manzitti C, Mora J, Vaz-Salgado MA, Luksch R, Mata C, Pierini M, Carretta E, Cesari M, Paioli A, Marrari A, Scotlandi K, Serra M, Asaftei SD, Gambarotti M, Picci P, Ferrari S, Valverde C, Ibrahim T, Broto JM. Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials. J Clin Oncol. 2025 Oct;43(28):3113-3122. doi: 10.1200/JCO-25-00210. Epub 2025 Aug 18.
PMID: 40825172DERIVEDPalmerini E, Meazza C, Tamburini A, Bisogno G, Ferraresi V, Asaftei SD, Milano GM, Coccoli L, Manzitti C, Luksch R, Serra M, Gambarotti M, Donati DM, Scotlandi K, Bertulli R, Favre C, Longhi A, Abate ME, Perrotta S, Mascarin M, D'Angelo P, Cesari M, Staals EL, Marchesi E, Carretta E, Ibrahim T, Casali PG, Picci P, Fagioli F, Ferrari S. Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2). Cancer. 2022 May 15;128(10):1958-1966. doi: 10.1002/cncr.34131. Epub 2022 Feb 24.
PMID: 35201621DERIVEDHattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PMID: 31401903DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Emanuela Palmerini, MD
Istituto Ortopedico Rizzoli
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 19, 2011
First Posted
October 25, 2011
Study Start
June 23, 2011
Primary Completion
April 30, 2024
Study Completion
April 30, 2024
Last Updated
May 20, 2024
Record last verified: 2024-05