Clinical trial NCT01459484: ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma
Official title: ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma - Prospective Study (ISG/OS-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteosarcoma
Keywords: Non metastatic extremities high grade osteosarcoma
Lead sponsor: Italian Sarcoma Group
Sponsor class: NETWORK
First posted: 2011-10-25
Enrollment: 225
Sex: ALL
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Events free survival
timeFrame: 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:
measure: Overall Survival
timeFrame: 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).
Other outcomes:
Locations:
city: Candiolo
country: Italy
facility: I.R.C.C. - Unit of Medical Oncology
state: Torino
city: Torino
country: Italy
facility: Presidio Sanitario Gradenigo
state: TO
city: Bologna
country: Italy
facility: IRCCS Istituto ortopedico Rizzoli
city: Firenze
country: Italy
facility: A.O. Universitaria Meyer
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Milano
country: Italy
facility: FONDAZIONE IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori "Fondazione G. Pascale"
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri di Roma
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambin Gesu'
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
Study officials:
affiliation: Istituto Ortopedico Rizzoli
name: Emanuela Palmerini, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Palmerini 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.
citation: Hattinger 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.