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Osteosarcoma | Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?

Osteosarcoma research study

What is the primary objective of this study?

Methotrexate is one of the most effective chemotherapy drugs in the treatment of osteosarcoma and some other types of bone sarcoma which are treated the same way as osteosarcoma. However, it frequently leads to sore mouth, tummy pain and increased risk of developing infections. The investigators try to save or \"rescue\" normal cells from the side effects of methotrexate by giving a drug called folinic acid. Folinic acid is started 24 hours after methotrexate and given regularly until methotrexate levels are really low and not dangerous to normal cells anymore. Despite this rescue, side effects are still a problem and many patients are not well enough to receive subsequent chemotherapy on time. Almost half of the planned chemotherapy cycles are not given on time due to methotrexate side effects. In this study the investigators will examine if adding a drug called glucarpidase to folinic acid is helpful. Glucarpidase is an enzyme that inactivates methotrexate in the blood stream. Lower methotrexate concentration in the blood stream leads to fewer side effects. The investigators would like to see if glucarpidase helps patients to have their chemotherapy on time, by reducing the side effects of methotrexate.

Who is eligible to participate?

Inclusion Criteria: Written informed consent from patient or parent/guardian Diagnosis of high grade osteosarcoma, localised or metastatic or high grade osteosarcoma as a second malignancy or spindle cell sarcoma of bone or relapsed high grade osteosarcoma Ability to comply with study and follow up procedures (WHO performance scale 0-2) No concomitant anti-cancer or investigational drugs during the study and complete resolution of toxicity related to previous treatment Life expectancy of at least 3 months Haematopoietic function: Absolute neutrophil count ≥1 x109/L, Platelets ≥75 x109/L Hepatic function: Bilirubin ≤1.5 x ULN Renal function: Glomerular Filtration Rate (radioisotope) ≥ 70 ml/min/1.73m2 Exclusion Criteria: Previous treatment with glucarpidase Pregnant or breast feeding women (patients with reproductive potential of either gender must use contraception*) Concomitant treatment with agents which interact with methotrexate metabolism or excretion Serous effusions, including ascites and pleural effusions

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Osteosarcoma

Spindle Cell Sarcoma of Bone

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:GlucarpidaseGlucarpidase rescue (50 units/kg x 1, intravenously)

Drug:MethotrexateMethotrexate (12 g/m2 x 1, intravenously)

Drug:Folinic AcidFolinic acid rescue 15mg/m2 four times daily adjusted according to methotrexate levels

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

MMethotrexate (12 g/m2 x 1, intravenously) with standard folinic acid rescue In arm A patients will receive cycle M first followed by cycle GluM. Cycle M starts with course M1 on day 1 followed by course M2 planned for day 8. Cycle GluM starts with course GluM1 on day 1 followed by GluM2 planned for day 8. Cycle GluM will not start for a minimum of 14 days from the beginning of course M2, or until bone marrow, renal and hepatic functions have completely recovered and the patient is clinically ready to receive further chemotherapy .

GluMMethotrexate (12 g/m2 x 1, intravenously) with folinic acid and glucarpidase rescue (50 units/kg x 1, intravenously). In arm B, patients will receive cycle GluM first followed by cycle M. Cycle GluM starts with course GluM1 on day 1 followed by GluM2 planned for day 8.Cycle M starts with course M1 on day 1 followed by course M2 planned for day 8. Cycle M will not start for a minimum of 14 days from the beginning of course GluM2, or until bone marrow, renal and hepatic function have completely recovered and the patient is clinically ready to receive further chemotherapy

Study Status

Terminated

Start Date: July 2007

Completed Date: June 2015

Phase: Phase 2

Type: Interventional

Design:

Primary Outcome: Estimate of the difference in proportions of patients ready to receive chemotherapy on Day 15 of each chemotherapy cycle comparing standard rescue and glucarpidase+standard rescue

Secondary Outcome: To investigate whether glucarpidase rescue after high-dose methotrexate reduces the incidence of methotrexate associated adverse effects

Study sponsors, principal investigator, and references

Principal Investigator: Jeremy Whelan, Professor

Lead Sponsor: University College, London

Collaborator: Richard Scowcroft Foundation

More information:https://clinicaltrials.gov/show/NCT02022358

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