ABCB1/P-glycoprotein Expression Influence on Non-metastatic Osteosarcoma of the Extremities

NCT ID: NCT04383288

Last Updated: 2021-08-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

115 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-07-02

Study Completion Date

2020-10-17

Brief Summary

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Post-authorization, observational, multicenter and prospective study in patients between 2 and 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.

All patients included in the study will receive the initial neoadjuvant treatment prescribed by the doctor of each center, according to standard practice (involving methotrexate, cisplatin, and adriamycin). This initial treatment precedes surgical treatment.

After surgical treatment, the histological response to neoadjuvant chemotherapy will be evaluated. The histological response to primary chemotherapy will be expressed as a percentage of tumor necrosis. In the case of tumor necrosis above 90% the patient is defined as a "good responder" in case of a lower percentage as a "poor responder".

As an adjuvant treatment, the following options may be given according to standard practice in each center:

1. \- If there is overexpression of ABCB1 / P-glycoprotein and poor response to induction treatment, in many sites ifosfamide at high doses and MTP-PE, is incorporated in addition to adriamycin.
2. \- If there is overexpression of ABCB1 / P-glycoprotein and a good response to induction treatment, in many centers the option of additional administration of methotrexate, CDDP and adriamycin will be chosen.
3. \- If there is no overexpression of ABCB1 / P-glycoprotein, the administration of methotrexate, adriamycin and cisplatin will be chosen in many sites.

In some sites they will consider the non-administration of MTP-PE or the non-administration of high doses of ifosfamide. And, in some hospitals, they will consider administering MTP-PE to all patients.

Detailed Description

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The Primary objective is:

\- Disease-free survival measured as a 5-year rate in patients with localized osteosarcoma treated, according to standard practice, with all the drugs currently registered for the treatment of non-metastatic osteosarcoma (methotrexate, cisplatin, adriamycin, ifosfamide, MTP-PE), according to ABCB1 / P-glycoprotein expression.

The Secondary objectives are:

* Evaluate overall survival in a homogeneous population of patients with non-metastatic osteosarcoma.
* Disease-free survival at 2 and 3 years.

Conditions

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Osteosarcoma

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Overexpression of ABCB1 / P-glycoprotein. Poor response

If there is overexpression of ABCB1 / P-glycoprotein and poor response to induction treatment, in many sites ifosfamide at high doses and MTP-PE (Muramyl tripeptide phosphatidylethanolamine), is incorporated in addition to adriamycin.

BEFORE SURGERY TREATMENT:

Methotrexate: 12g/m2 (3 cycles) Cisplatinum: 120mg/m2 (3 cycles) Doxorubicin: ADM (Adriamycin) 75mg/m2 (3 cycles)

AFTER 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 length treatment 44 weeks)

All the product are used as commercial formulation

Other Names:

Methotrexate Cisplatinum doxorubicin ifosfamide mifamurtide

No interventions assigned to this group

Overexpression of ABCB1 / P-glycoprotein. Good response

If there is overexpression of ABCB1 / P-glycoprotein and a good response to induction treatment, in many centers the option of additional administration of methotrexate, CDDP (Cisplatinum) and adriamycin will be chosen.

BEFORE SURGERY TREATMENT:

Methotrexate: 12g/m2 (3 cycles) Cisplatinum: 120mg/m2 (3 cycles) Doxorubicin: ADM 75mg/m2 (3 cycles)

AFTER 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 length treatment 44 weeks)

All the product are used as commercial formulation

Other Names:

Methotrexate Cisplatinum doxorubicin ifosfamide mifamurtide

No interventions assigned to this group

No overexpression of ABCB1 / P-glycoprotein

If there is no overexpression of ABCB1 / P-glycoprotein, the administration of methotrexate, adriamycin and cisplatin will be chosen in many sites.

BEFORE SURGERY TREATMENT:

Methotrexate: 12g/m2 (3 cycles) Cisplatinum: 120mg/m2 (3 cycles) Doxorubicin: ADM 75mg/m2 (3 cycles)

AFTER SURGERY TREATMENT:

Methotrexate 12g/m2 (10 cycles) Cisplatinum 120mg/m2; Doxorubicin 90mg/m2

Total length 34 weeks

All the product are used as commercial formulation

Other Names:

methotrexate cisplatin doxorubicine

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Confirmed histological diagnosis of high-grade osteosarcoma of the extremities.
2. Age: from 2 to 30 years old.
3. Localized disease (metastasis skip accepted).
4. Normal liver, kidney and spinal function.
5. Ventricular ejection fraction of 50%.
6. Absence of previous surgical treatments or chemotherapy for osteosarcoma.
7. Interval between histological diagnosis and initiation of chemotherapy not exceeding 4 weeks.
8. Signing of the consent form to participate in the study.

Exclusion Criteria

1. Presence of lung metastases on chest CT or in other locations.
2. Parosteal, periosteal, or secondary osteosarcoma.
3. Contraindications of the medications prescribed in the protocol.
4. Pregnant or lactating.
5. Mental or social conditions that do not guarantee adequate adherence to the protocol.
6. Not having an adequate understanding of study participation.
Minimum Eligible Age

12 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Grupo Espanol de Investigacion en Sarcomas

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Óscar Gallego, Dr.

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Luis Gros, Dr.

Role: PRINCIPAL_INVESTIGATOR

Hospital Vall d'Hebron

Locations

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Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, Spain

Site Status

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Site Status

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Site Status

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Site Status

Hospital Universitario Cruces

Barakaldo, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario Infantil Niño Jesús

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Regional Universitario de Málaga

Málaga, , Spain

Site Status

Hospital Universitari Son Espases

Palma de Mallorca, , Spain

Site Status

Hospital Universitario de Canarias

San Cristóbal de La Laguna, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Countries

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Spain

References

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Palmerini E, Meazza C, Tamburini A, Marquez-Vega C, Bisogno G, Fagioli F, Ferraresi V, Milano GM, Coccoli L, Rubio-San-Simon A, Gallego O, Llinares Riestra ME, Manzitti C, Mora J, Vaz-Salgado MA, Luksch R, Mata C, Pierini M, Carretta E, Cesari M, Paioli A, Marrari A, Scotlandi K, Serra M, Asaftei SD, Gambarotti M, Picci P, Ferrari S, Valverde C, Ibrahim T, Broto JM. Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials. J Clin Oncol. 2025 Oct;43(28):3113-3122. doi: 10.1200/JCO-25-00210. Epub 2025 Aug 18.

Reference Type DERIVED
PMID: 40825172 (View on PubMed)

Other Identifiers

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GEIS-33

Identifier Type: -

Identifier Source: org_study_id

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