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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Italian Sarcoma Group
Sponsor:
Information provided by (Responsible Party):
Italian Sarcoma Group
ClinicalTrials.gov Identifier:
NCT01459484
First received: October 19, 2011
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Osteosarcoma
Drug: Mifamurtide arm
Other: 3 drugs arm
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Italian Sarcoma Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: The patients will be followed in term of Overall Survival, for all the study period (expected average: 7 years) ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 225
Study Start Date: July 2011
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459484

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 Not yet recruiting
Milano, Italy
Contact: Rossella Bertulli, MD         
Principal Investigator: Rossella Bertulli, MD         
FONDAZIONE IRCCS Istituto Nazionale dei Tumori Not yet 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 Not yet recruiting
Padova, Italy
Contact: Gianni Bisogno, MD         
Principal Investigator: Gianni Bisogno, MD         
Istituti Fisioterapici Ospitalieri di Roma Not yet recruiting
Roma, Italy
Contact: Virginia Ferraresi, MD         
Principal Investigator: Virginia Ferraresi, MD         
Ospedale Pediatrico Bambin Gesu' Not yet recruiting
Roma, Italy
Contact: Raffaele Cozza, MD         
Principal Investigator: Raffaele Cozza, MD         
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology Not yet 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

Publications:
Responsible Party: Italian Sarcoma Group
ClinicalTrials.gov Identifier: NCT01459484     History of Changes
Other Study ID Numbers: ISG/OS-2, 2011-001659-36
Study First Received: October 19, 2011
Last Updated: October 14, 2013
Health Authority: Italy: Ethics Committee

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
Liposomal doxorubicin
Krestin
Isophosphamide mustard
Cisplatin
Doxorubicin
Ifosfamide
Methotrexate
Mifamurtide
Acetylmuramyl-Alanyl-Isoglutamine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 19, 2014