OsteosarcomaNCT04383288
ABCB1/P-glycoprotein Expression Influence on Non-metastatic Osteosarcoma of the Extremities
An observational study of Osteosarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 17 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 30 years
- Conditions the study is for
- Osteosarcoma
- How many people
- 115 participants
- Where
- 17 sitesSpain
- Study dates
- 2 Jul 2014to 17 Oct 2020
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 30 years
- All sexes
- Child, Adult
Study population: Patients from 2 to 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Spain17 sites
Hospital Universitario Cruces
Barakaldo
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia
Hospital General Universitario Gregorio Marañón
Madrid
Hospital Universitario Infantil Niño Jesús
Madrid
Hospital Universitario La Paz
Madrid
Hospital Universitario Ramón y Cajal
Madrid
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid
Hospital Regional Universitario de Málaga
Málaga
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
Hospital Universitari Son Espases
Palma de Mallorca
Hospital Universitario de Canarias
San Cristóbal de La Laguna
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, A Coruña
Hospital Universitario Virgen del Rocío
Seville
Hospital Universitari i Politècnic La Fe
Valencia
Hospital Universitario Miguel Servet
Zaragoza
About this study
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
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.
Read more
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:
- - 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.
- - 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.
- - 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.
Read the 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.
- Conditions
- Osteosarcoma
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
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.
Measured: After 2 and 3 years from the start of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start2 Jul 2014
- Primary completion17 Oct 2020
- Study completion17 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 115 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Investigacion en Sarcomas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Óscar Gallego, Dr., Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauLuis Gros, Dr., Principal investigator, Hospital Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04383288
- Sponsor's protocol ID
- GEIS-33
- Status last verified
- Aug 2021
- First submitted
- 7 May 2020
- Last updated
- 4 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40825172
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04383288
- Acronym / sponsor ID
- GEIS-33
- Conditions
- Osteosarcoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- Grupo Espanol de Investigacion en SarcomasUniversity, hospital or other
- Study start
- 2 Jul 2014 (actual)
- Primary completion
- 17 Oct 2020 (actual)
- Study completion
- 17 Oct 2020 (actual)
- First posted
- 12 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- - 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.
- - 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.
- - 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 12 to 30 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- Patients from 2 to 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.
Key inclusion criteria (8 listed)
- 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%.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Overall Survival
Time frame: 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)
1 secondary outcome
Events free survival
Time frame: After 2 and 3 years from the start of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
- Derived from this study: PubMed 40825172Palmerini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Óscar Gallego, Dr. principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Luis Gros, Dr. principal investigator
Hospital Vall d'Hebron
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteosarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 17 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: The patients will be followed in term of Overall Survival, for all the study period (expected average: 7 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04383288, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2021.