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

Study Description

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Brief Summary:

The main objective of the study is to assess the survival in patient with non metastatic osteosarcoma of the extremities treated with different chemotherapy protocols, according to the expression of ABCB1/P-glycoprotein

Condition or disease	Intervention/treatment	Phase
Osteosarcoma	Drug: Mifamurtide arm; Other: 3 drugs arm	Phase 2; Phase 3

Detailed Description:

The Primary objective is:

* Overall survival in patient with non metastatic osteosarcoma of the extremities treated with different chemotherapy approach (5 drugs vs 3 drugs), according to the expression of ABCB1/P-glycoprotein

The Secondary objectives are:

• to assess the survival in patient who over express ABCB1/P-glycoprotein, with chemotherapy protocol based on all the 5 available active drugs (Methotrexate, cisplatinum, doxorubicine, ifosfamide and mifamurtide)
• to assess the survival in patient who do not over express ABCB1/P-glycoprotein

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	225 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma - Prospective Study (ISG/OS-2)
Study Start Date :	July 2011
Estimated Primary Completion Date :	January 2020
Estimated Study Completion Date :	February 2020

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Mifamurtide arm; Chemotherapy for patients who over express ABCB1/P-glycoprotein (methotrexate, cisplatinum, doxorubicine, ifosfamide + mifamurtide)	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 Names: Methotrexate; Cisplatinum; doxorubicin; ifosfamide; mifamurtide
3 drugs arm; High grade osteosarcoma treatment for patients who do not over express ABCB1/P-glycoprotein	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; Other Names: methotrexate; cisplatin; doxorubicine

Outcome Measures

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Primary Outcome Measures :

1. Overall Survival [ Time Frame: The patients will be followed in term of Overall Survival, for all the study period (expected average: 7 years) ]
   The Overall Survival will be evaluated at the end of the study period (5 enrollment years and 2 years - minimum- follow-up from the last enrolled patient)

Secondary Outcome Measures :

1. Events free survival in patient with ABCB1/P-glycoprotein over-expression, and who do not over-express ABCB1/P-glycoprotein [ Time Frame: after 2 and 3 years from the start of study ]
   The events free survival will be evaluated by means of interim analysis after 2 and 3 years from the start of study. A further evaluation will be performed at the end of enrollment and after 2 years form the last enrolled patient.

Eligibility Criteria

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Ages Eligible for Study:	up to 40 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Stefano Ferrari, MD	+390516366 ext 411	stefano.ferrari@ior.it
Contact: Emanuela Marchesi, PhD	+390516366 ext 400	emanuela.marchesi@ior.it

Locations

Italy
I.R.C.C. - Unit of Medical Oncology	Not yet recruiting
Candiolo, Torino, Italy, 10060
Contact: Giovanni Grignani, MD +39.011.9933 ext 278 giovanni.grignani@ircc.it
Contact: Luisa Gioeni, Pharmacist +39.011.9933 ext 278 luisa.gioeni@ircc.it
Sub-Investigator: Giovanni Grignani, MD
Principal Investigator: Massimo Aglietta, MD
Presidio Sanitario Gradenigo	Not yet recruiting
Torino, TO, Italy, 10153
Contact: Alessandro Comandone, MD +390118151 ext 211 alessandro.comandone@gradenigo.it
Principal Investigator: Alessandro Comandone, MD
Istituto Ortopedico Rizzoli	Recruiting
Bologna, Italy, 40136
Contact: Stefano Ferrari, MD +390516366 ext 411 stefano.ferrari@ior.it
Contact: Emanuela Marchesi, PhD +390516366 ext 400 emanuela.marchesi@ior.it
Principal Investigator: Stefano Ferrari, MD
A.O. Universitaria Meyer	Recruiting
Firenze, Italy, 50139
Contact: Angela Tamburini, MD +3905556 ext 621 a.tamburini@meyer.it
Principal Investigator: Angela Tamburini, MD
Istituto Giannina Gaslini	Not yet recruiting
Genova, Italy
Contact: Carla Manzitti, MD
Principal Investigator: Carla Manzitti, MD
FONDAZIONE IRCCS Istituto Nazionale dei Tumori	Recruiting
Milano, Italy
Contact: Rossella Bertulli, MD
Principal Investigator: Rossella Bertulli, MD
FONDAZIONE IRCCS Istituto Nazionale dei Tumori	Recruiting
Milano, Italy
Contact: Roberto Luksch, MD
Principal Investigator: Roberto Luksch, MD
Istituto Nazionale Tumori "Fondazione G. Pascale"	Not yet recruiting
Napoli, Italy, 80131
Contact: Gaetano Apice, MD
Principal Investigator: Gaetano Apice, MD
Azienda Ospedaliera di Padova	Recruiting
Padova, Italy
Contact: Gianni Bisogno, MD
Principal Investigator: Gianni Bisogno, MD
Istituti Fisioterapici Ospitalieri di Roma	Recruiting
Roma, Italy
Contact: Virginia Ferraresi, MD
Principal Investigator: Virginia Ferraresi, MD
Ospedale Pediatrico Bambin Gesu'	Recruiting
Roma, Italy
Contact: Raffaele Cozza, MD
Principal Investigator: Raffaele Cozza, MD
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology	Recruiting
Torino, Italy, 10126
Contact: Franca Fagioli, MD +39.011.3135 ext 230 franca.fagioli@unito.it
Principal Investigator: Franca Fagioli, MD

Sponsors and Collaborators

Italian Sarcoma Group

Investigators

Principal Investigator:	Stefano Ferrari, MD	Italian Sarcoma Group

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

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.

Responsible Party:	Italian Sarcoma Group
ClinicalTrials.gov Identifier:	NCT01459484 History of Changes
Other Study ID Numbers:	ISG/OS-2; 2011-001659-36 ( EudraCT Number )
First Posted:	October 25, 2011
Last Update Posted:	April 11, 2018
Last Verified:	April 2018

Keywords provided by Italian Sarcoma Group:

Non metastatic extremities high grade osteosarcoma

Additional relevant MeSH terms:

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Doxorubicin; Liposomal doxorubicin; Krestin; Isophosphamide mustard; Methotrexate; Ifosfamide; Cisplatin; Mifamurtide

Acetylmuramyl-Alanyl-Isoglutamine; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists