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

NCT04383288 | Completed

• 1 other identifier: GEIS-33
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 17

Brief Summary

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

Conditions

Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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)

  The patients will be followed in term of Overall Survival, for all the study period (expected average: 7 years)

Secondary Outcomes (1)

• Events free survival

  After 2 and 3 years from the start of study

Study Arms (3)

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

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 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

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients from 2 to 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (17)

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitario Cruces

Barakaldo, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario Infantil Niño Jesús

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Related Publications (1)

• 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.

  PMID: 40825172 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA from peripheral blood samples.

MeSH Terms

Conditions

Osteosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Óscar Gallego, Dr.

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

  PRINCIPAL INVESTIGATOR

• Luis Gros, Dr.

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 12, 2020
• Study Start: July 2, 2014
• Primary Completion: October 17, 2020
• Study Completion: October 17, 2020
• Last Updated: August 4, 2021

Record last verified: 2021-08

Locations

ES (17)