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Clinical Trial Evaluating Metronomic Chemotherapy in Patients With Metastatic Osteosarcoma

Phase 2
Conditions
Osteosarcoma
Interventions
Registration Number
NCT03063983
Lead Sponsor
Grupo de Apoio ao Adolescente e a Crianca com Cancer
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).

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
158
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Maintenance therapyCyclophosphamide104 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP
Maintenance therapyMethotrexate104 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Efficacy and toxicity of adding metronomic therapy in overall survivalFive 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

Trial Locations

Locations (1)

Grupo de Apoio ao Adolescente e a Criança com Câncer

🇧🇷

Sao Paulo, Brazil

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