Clinical trial NCT03063983: Clinical Trial Evaluating Metronomic Chemotherapy in Patients With Metastatic Osteosarcoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Osteosarcoma
Keywords: osteosarcoma
metastatic
metronomic therapy
Lead sponsor: Grupo de Apoio ao Adolescente e a Crianca com Cancer
Sponsor class: OTHER
First posted: 2017-02-24
Enrollment: 158
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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\> 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.

Primary outcomes:
measure: Efficacy and toxicity of adding metronomic therapy in disease event-free survival.
timeFrame: Five years
Secondary outcomes:
measure: Efficacy and toxicity of adding metronomic therapy in overall survival
timeFrame: Five years
measure: Cardiotoxicity (occurrence of cardiotoxicity)
timeFrame: Five years
measure: Immunohistochemistry (expression of VEGF)
timeFrame: Five years
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Grupo de Apoio ao Adolescente e a Criança com Câncer
Study officials:
affiliation: Grupo de Apoio ao Adolescente e a Crianca com Cancer
name: Cláudia F Fontes
role: STUDY_CHAIR
References: