Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?
Information source: University College, London
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteosarcoma; Spindle Cell Sarcoma of Bone
Intervention: Glucarpidase (Drug); Methotrexate (Drug); Folinic Acid (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: University College, London Official(s) and/or principal investigator(s): Jeremy Whelan, Professor, Principal Investigator, Affiliation: University College London Hospitals
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.
Clinical Details
Official title: 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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
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 effectsPlasma methotrexate concentration Incidence of glucarpidase related adverse effects Number of days required in hospital per cycle Assessment of quality of life Serum anti-glucarpidase IgG levels following glucarpidase administration To investigate whether glucarpidase rescue after high-dose methotrexate reduces the severity of methotrexate associated adverse effects To investigate whether glucarpidase rescue after high-dose methotrexate reduces the duration of methotrexate associated adverse effects Plasma DAMPA concentration Total dose of folinic acid rescue required per cycle
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.
Eligibility
Minimum age: 5 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
University College Hospital, London NW1 2PG, United Kingdom
Additional Information
Starting date: July 2007
Last updated: June 3, 2015
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