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

May 17, 2024 updated by: Italian Sarcoma Group

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

225

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 40136
        • IRCCS Istituto Ortopedico Rizzoli
      • Firenze, Italy, 50139
        • A.O. Universitaria Meyer
      • Genova, Italy
        • Istituto Giannina Gaslini
      • Milano, Italy
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori "Fondazione G. Pascale"
      • Padova, Italy
        • Azienda Ospedaliera Di Padova
      • Roma, Italy
        • Ospedale Pediatrico Bambin Gesu'
      • Roma, Italy
        • Istituti Fisioterapici Ospitalieri di Roma
      • Torino, Italy, 10126
        • Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
    • TO
      • Torino, TO, Italy, 10153
        • Presidio Sanitario Gradenigo
    • Torino
      • Candiolo, Torino, Italy, 10060
        • I.R.C.C. - Unit of Medical Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 36 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Cisplatinum
  • Methotrexate
  • doxorubicin
  • ifosfamide
  • mifamurtide
Other: 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:
  • cisplatin
  • methotrexate
  • doxorubicine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Events free survival
Time Frame: 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).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 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).
Time elapsed for the diagnosis to the death for any cause or to 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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Italian Sarcoma Group

Investigators

  • Principal Investigator: Emanuela Palmerini, MD, Istituto Ortopedico Rizzoli

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 23, 2011

Primary Completion (Actual)

April 30, 2024

Study Completion (Actual)

April 30, 2024

Study Registration Dates

First Submitted

October 19, 2011

First Submitted That Met QC Criteria

October 24, 2011

First Posted (Estimated)

October 25, 2011

Study Record Updates

Last Update Posted (Actual)

May 20, 2024

Last Update Submitted That Met QC Criteria

May 17, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISG/OS-2
  • 2011-001659-36 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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