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

Completed

• Conditions: Osteosarcoma

• Registration Number: NCT04383288
• Lead Sponsor: Grupo Espanol de Investigacion en Sarcomas

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. - 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

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.

Study Timeline

• Study Start: 2014-07-02
• Study First Submitted: 2020-05-07
• Study First Submitted QC: 2020-05-07
• Study First Posted: 2020-05-12
• Primary Completion: 2020-10-17
• Study Completion: 2020-10-17
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-03
• Last Update Posted: 2021-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 115

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Events free survival	After 2 and 3 years from the start of study	The events free survival will be evaluated by means of interim analysis after 2 and 3 years from the start of study. A further evaluation will be performed at the end of enrollment and after 2 years form the last enrolled patient.

Trial Locations

Locations (17)

Complejo Hospitalario Universitario de Santiago; 🇪🇸 Santiago De Compostela, A Coruña, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Universitario Puerta de Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Hospital Universitario Virgen de la Arrixaca; 🇪🇸 El Palmar, Murcia, Spain

Hospital Universitario Cruces; 🇪🇸 Baracaldo, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario de Canarias; 🇪🇸 La Laguna, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario Infantil Niño Jesús; 🇪🇸 Madrid, Spain

Scroll for more (7 remaining)