Osteosarcoma
Conditions
Keywords
osteosarcoma, metastatic, metronomic therapy
Brief summary
Preclinical models show that a daily antiangiogenic regimen at low-dose may be effective against chemotherapy-resistant tumors. The aim of this study is to evaluate the efficacy of maintenance therapy with continuous oral cyclophosphamide and methotrexate in patients with high grade, operable, metastatic osteosarcoma (OST) of the extremities. The primary end point is event-free survival (EFS) from randomization
Detailed description
The study design includes backbone of 10 weeks of preoperative therapy using MAP (high-dose methotrexate, cisplatin, doxorubicin and dexrazoxane). Metastatic patients were randomized to high-dose chemotherapy for 31 weeks (arm 1) or concomitant metronomic therapy (MTX plus cyclophosphamide) such as 31 weeks of high-dose chemotherapy, followed by 73 weeks of metronomic therapy after completion of high-dose chemotherapy, totaling 104 weeks of metronomic therapy (arm 2).
Interventions
DRUGCyclophosphamide
Continuous oral cyclophosphamide
DRUGMethotrexate
Continuous oral methotrexate
Sponsors
Grupo de Apoio ao Adolescente e a Crianca com Cancer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 30 Years
Healthy volunteers
No
Inclusion criteria
* A newly diagnosed patient, previously untreated, with a high degree of malignancy, confirmed by biopsy. Participant with OST as a neoplasm are also eligible * Participant with staging imaging studies performed less than four weeks. Otherwise, it should be re-staged * If pre-chemotherapy amputation is necessary, the participant will enter the study being excluded from the evaluation of tumor necrosis grade according to Huvos, but eligible for survival analysis * Participant aged ≥ 16 years should have a Karnofsky performance score\> 50 or WHO / ECOG ≥ 2 and patients \<16 years should have a Lansky performance score\> 50. Participant with a performance score impaired by the presence of a pathological fracture are eligible * Patients with normal organic function * Sexually active participant should agree to use contraceptive methods throughout the treatment * Female participant should have a negative pregnancy test
Exclusion criteria
* If the participant or their legal guardian refuses to sign the informed consent form / consent term it will not be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy and toxicity of adding metronomic therapy in disease event-free survival. | Five years | To assess the impact of adding metronome therapy to the standard treatment of patients with resectable end-stage osteosarcoma and metastatic lung disease in event-free survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy and toxicity of adding metronomic therapy in overall survival | Five years | To evaluate the impact of the addition of metronomic therapy to the standard treatment of patients with end-resectable osteosarcoma and metastatic lung disease in overall survival. |
| Cardiotoxicity (occurrence of cardiotoxicity) | Five years | To compare the occurrence of cardiotoxicity with the addition of dexrazoxane since the first cycle of doxorubicin with the findings of the previous study (GLATO 2006). |
| Immunohistochemistry (expression of VEGF) | Five years | Immunohistochemistry the expression of VEGF in the biopsy, primary tumor and metastases |
Countries
Brazil
Contacts
Primary ContactAntonio S Petrilli
Backup ContactAndreza A Senerchia
Outcome results
None listed