Clinical Trial Evaluating Metronomic Chemotherapy in Patients With Metastatic Osteosarcoma

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Osteosarcoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maintenance therapy<br>104 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP | Drug: Cyclophosphamide<br>* Continuous oral cyclophosphamide<br>Drug: Methotrexate<br>* Continuous oral methotrexate<br>|
| No Intervention: Control<br>31 weeks of MAP | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy and toxicity of adding metronomic therapy in disease event-free survival. | 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. | Five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy and toxicity of adding metronomic therapy in overall survival | 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. | Five years | 
| Cardiotoxicity (occurrence of cardiotoxicity) | 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). | Five years | 
| Immunohistochemistry (expression of VEGF) | Immunohistochemistry the expression of VEGF in the biopsy, primary tumor and metastases | Five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteosarcoma, metastatic, metronomic therapy