Clinical trial NCT04383288: ABCB1/P-glycoprotein Expression Influence on Non-metastatic Osteosarcoma of the Extremities
Official title: Prospective Observational Study of the Expression of ABCB1 / P-glycoprotein as a Factor for the Biological Stratification of Non-metastatic Osteosarcoma of the Extremities
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Osteosarcoma
Lead sponsor: Grupo Espanol de Investigacion en Sarcomas
Sponsor class: OTHER
First posted: 2020-05-12
Enrollment: 115
Sex: ALL
Minimum age (years): 12
Maximum age (years): 30
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients from 2 to 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: The patients will be followed in term of Overall Survival, for all the study period (expected average: 7 years)
Secondary outcomes:
measure: Events free survival
timeFrame: After 2 and 3 years from the start of study
Other outcomes:
Locations:
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
state: A Coruña
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
state: Murcia
city: Baracaldo
country: Spain
facility: Hospital Universitario Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Infantil Niño Jesús
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Espases
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Óscar Gallego, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Vall d'Hebron
name: Luis Gros, Dr.
role: PRINCIPAL_INVESTIGATOR
References: