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

Sponsor

Italian Sarcoma Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01459484

Collaborator

(none)

225

Enrollment

Locations

Arms

124.3

Anticipated Duration (Months)

20.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Osteosarcoma	Drug: Mifamurtide arm Other: 3 drugs arm	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

225 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel 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)

Actual Study Start Date :

Jun 23, 2011

Anticipated Primary Completion Date :

Oct 30, 2021

Anticipated Study Completion Date :

Oct 30, 2021

Arms and Interventions

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
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: methotrexate cisplatin doxorubicine

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

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:

methotrexate

cisplatin

doxorubicine

Outcome Measures

Primary Outcome Measures

Events free survival [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

Secondary Outcome Measures

Overall Survival [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 40 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	I.R.C.C. - Unit of Medical Oncology	Candiolo	Torino	Italy	10060
2	Presidio Sanitario Gradenigo	Torino	TO	Italy	10153
3	IRCCS Istituto ortopedico Rizzoli	Bologna		Italy	40136
4	A.O. Universitaria Meyer	Firenze		Italy	50139
5	Istituto Giannina Gaslini	Genova		Italy
6	FONDAZIONE IRCCS Istituto Nazionale dei Tumori	Milano		Italy
7	Istituto Nazionale Tumori "Fondazione G. Pascale"	Napoli		Italy	80131
8	Azienda Ospedaliera di Padova	Padova		Italy
9	Istituti Fisioterapici Ospitalieri di Roma	Roma		Italy
10	Ospedale Pediatrico Bambin Gesu'	Roma		Italy
11	Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology	Torino		Italy	10126