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

Primary Purpose

Osteosarcoma

Status
Active
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Mifamurtide arm
3 drugs arm
Sponsored by
Italian Sarcoma Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteosarcoma focused on measuring Non metastatic extremities high grade osteosarcoma

Eligibility Criteria

undefined - 40 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • I.R.C.C. - Unit of Medical Oncology
  • Presidio Sanitario Gradenigo
  • IRCCS Istituto ortopedico Rizzoli
  • A.O. Universitaria Meyer
  • Istituto Giannina Gaslini
  • FONDAZIONE IRCCS Istituto Nazionale dei Tumori
  • Istituto Nazionale Tumori "Fondazione G. Pascale"
  • Azienda Ospedaliera di Padova
  • Istituti Fisioterapici Ospitalieri di Roma
  • Ospedale Pediatrico Bambin Gesu'
  • Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Mifamurtide arm

3 drugs arm

Arm Description

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

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

Outcomes

Primary Outcome Measures

Events free survival
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

Secondary Outcome Measures

Overall Survival
Time elapsed for the diagnosis to the death for any cause or to the last follow-up examination.

Full Information

First Posted
October 19, 2011
Last Updated
October 3, 2023
Sponsor
Italian Sarcoma Group
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1. Study Identification

Unique Protocol Identification Number
NCT01459484
Brief Title
ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma
Acronym
ISG/OS-2
Official Title
ABCB1/P-glycoprotein Expression as Biologic Stratification Factor for Patients With Non Metastatic Osteosarcoma - Prospective Study (ISG/OS-2)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 23, 2011 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Italian Sarcoma Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma
Keywords
Non metastatic extremities high grade osteosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
225 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mifamurtide arm
Arm Type
Experimental
Arm Description
Chemotherapy for patients who over express ABCB1/P-glycoprotein (methotrexate, cisplatinum, doxorubicine, ifosfamide + mifamurtide)
Arm Title
3 drugs arm
Arm Type
Other
Arm Description
High grade osteosarcoma treatment for patients who do not over express ABCB1/P-glycoprotein
Intervention Type
Drug
Intervention Name(s)
Mifamurtide arm
Other Intervention Name(s)
Methotrexate, Cisplatinum, doxorubicin, ifosfamide, mifamurtide
Intervention Description
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
Other
Intervention Name(s)
3 drugs arm
Other Intervention Name(s)
methotrexate, cisplatin, doxorubicine
Intervention Description
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
Primary Outcome Measure Information:
Title
Events free survival
Description
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
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).
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Time elapsed for the diagnosis to the death for any cause or to the last follow-up examination.
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).

10. Eligibility

Sex
All
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emanuela Palmerini, MD
Organizational Affiliation
Istituto Ortopedico Rizzoli
Official's Role
Principal Investigator
Facility Information:
Facility Name
I.R.C.C. - Unit of Medical Oncology
City
Candiolo
State/Province
Torino
ZIP/Postal Code
10060
Country
Italy
Facility Name
Presidio Sanitario Gradenigo
City
Torino
State/Province
TO
ZIP/Postal Code
10153
Country
Italy
Facility Name
IRCCS Istituto ortopedico Rizzoli
City
Bologna
ZIP/Postal Code
40136
Country
Italy
Facility Name
A.O. Universitaria Meyer
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Istituto Giannina Gaslini
City
Genova
Country
Italy
Facility Name
FONDAZIONE IRCCS Istituto Nazionale dei Tumori
City
Milano
Country
Italy
Facility Name
Istituto Nazionale Tumori "Fondazione G. Pascale"
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Azienda Ospedaliera di Padova
City
Padova
Country
Italy
Facility Name
Istituti Fisioterapici Ospitalieri di Roma
City
Roma
Country
Italy
Facility Name
Ospedale Pediatrico Bambin Gesu'
City
Roma
Country
Italy
Facility Name
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
City
Torino
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
17088985
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.
Results Reference
background
PubMed Identifier
35201621
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.
Results Reference
derived
PubMed Identifier
31401903
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.
Results Reference
derived

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

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