NCT02022358

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

A Randomised, Cross-over Phase II Study to Investigate the Efficacy and Safety of Glucarpidase for Routine Use After High Dose Methotrexate in Patients With Bone Sarcoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 5 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

In this study the patient will receive 4 courses of high-dose methotrexate. High-dose methotrexate is normally given at weekly intervals, in blocks of two.The first two courses will be given on weeks 1 \& 2; the second two courses on weeks 4 \& 5. Two courses will be given with folinic acid rescue (standard high-dose methotrexate), and the other two will be given with glucarpidase rescue as well as folinic acid. This will enable us to compare whether there is any difference in side effects with and without glucarpidase and also how quickly patients recover from them. Half of the patients will receive standard high-dose methotrexate on weeks 1 \& 2 and high-dose methotrexate with glucarpidase on weeks 4 \& 5 (arm A) and half of the patients will first have high-dose methotrexate with glucarpidase on weeks 1 \& 2 and then standard high-dose methotrexate on weeks 4 \& 5 (arm B). All patients receiving methotrexate have daily blood tests to monitor the levels of methotrexate in their body, and monitor their kidney function. However, patients on this study will have extra blood tests for chemotherapy drug levels and glucarpidase antibody levels. During each hospital admission for chemotherapy, blood samples will be taken as follows: Day 1: Just before starting methotrexate (extra blood test) and at the end of methotrexate infusion (extra blood test) Day 2: 24 hours after starting methotrexate (routine blood test) and 20 minutes after the 24-hour blood test (i.e. just after the glucarpidase/placebo infusion) (extra blood test) Day 3+: Routine daily blood tests until the body has got rid of the methotrexate Extra blood samples will also be taken 15 days after starting each cycle and 1 month, 3 and 6 months, after starting the second cycle. Patients will also be asked to complete mucositis assessment and quality of life questionnaires.

Conditions

• Osteosarcoma
• Spindle Cell Sarcoma of Bone

Interventions

Type	Name	Description
DRUG	Glucarpidase	Glucarpidase rescue (50 units/kg x 1, intravenously)
DRUG	Methotrexate	Methotrexate (12 g/m2 x 1, intravenously)
DRUG	Folinic Acid	Folinic acid rescue 15mg/m2 four times daily adjusted according to methotrexate levels

Timeline

• Start date: 2007-07-01
• Primary completion: 2015-06-01
• Completion: 2015-06-01
• First posted: 2013-12-27
• Last updated: 2015-06-04

Locations

1 site across 1 country: United Kingdom