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

NCT ID: NCT01459484

Last Updated: 2024-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-23

Study Completion Date

2024-04-30

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

Conditions

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Osteosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Mifamurtide arm

Chemotherapy for patients who over express ABCB1/P-glycoprotein (methotrexate, cisplatinum, doxorubicine, ifosfamide + mifamurtide)

Group Type EXPERIMENTAL

Mifamurtide arm

Intervention Type DRUG

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 arm

High grade osteosarcoma treatment for patients who do not over express ABCB1/P-glycoprotein

Group Type OTHER

3 drugs arm

Intervention Type OTHER

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

Interventions

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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

Intervention Type DRUG

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

Intervention Type OTHER

Other Intervention Names

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Methotrexate Cisplatinum doxorubicin ifosfamide mifamurtide methotrexate cisplatin doxorubicine

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
Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Italian Sarcoma Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emanuela Palmerini, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Ortopedico Rizzoli

Locations

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

Candiolo, Torino, Italy

Site Status

Presidio Sanitario Gradenigo

Torino, TO, Italy

Site Status

IRCCS Istituto ortopedico Rizzoli

Bologna, , Italy

Site Status

A.O. Universitaria Meyer

Florence, , Italy

Site Status

Istituto Giannina Gaslini

Genova, , Italy

Site Status

FONDAZIONE IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Istituto Nazionale Tumori "Fondazione G. Pascale"

Napoli, , Italy

Site Status

Azienda Ospedaliera di Padova

Padua, , Italy

Site Status

Istituti Fisioterapici Ospitalieri di Roma

Roma, , Italy

Site Status

Ospedale Pediatrico Bambin Gesu'

Roma, , Italy

Site Status

Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

Torino, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 17088985 (View on PubMed)

Palmerini 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.

Reference Type DERIVED
PMID: 40825172 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35201621 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31401903 (View on PubMed)

Other Identifiers

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2011-001659-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISG/OS-2

Identifier Type: -

Identifier Source: org_study_id

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