A Study Multicenter Randomized to Assess the Efficacy and Toxicity of Adding Metronomic Therapy to the Standard Treatment of Patients With High Grade Malignant Osteosarcoma With Metastatic Lung Disease at Diagnosis and Primary Resectable Tumor: A Study by the Latin American Group for Treatment of Osteosarcoma
Overview
- Phase
- Phase 2
- Intervention
- Cyclophosphamide
- Conditions
- Osteosarcoma
- Sponsor
- Grupo de Apoio ao Adolescente e a Crianca com Cancer
- Enrollment
- 158
- Locations
- 1
- Primary Endpoint
- Efficacy and toxicity of adding metronomic therapy in disease event-free survival.
- Last Updated
- 9 years ago
Overview
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).
Investigators
Antônio Sérgio Petrilli
Principal Investigator
Grupo de Apoio ao Adolescente e a Crianca com Cancer
Eligibility Criteria
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\>
- •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.
Arms & Interventions
Maintenance therapy
104 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP
Intervention: Cyclophosphamide
Maintenance therapy
104 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP
Intervention: Methotrexate
Outcomes
Primary Outcomes
Efficacy and toxicity of adding metronomic therapy in disease event-free survival.
Time Frame: 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 Outcomes
- Efficacy and toxicity of adding metronomic therapy in overall survival(Five years)
- Cardiotoxicity (occurrence of cardiotoxicity)(Five years)
- Immunohistochemistry (expression of VEGF)(Five years)