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

NCT02022358 | Terminated Phase 2 DMC

• 1 other identifier: 06/085
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteosarcoma; Spindle Cell Sarcoma of Bone

Keywords

Osteosarcoma; Methotrexate; Glucarpidase; Mucositis

Outcome Measures

Primary Outcomes (1)

• 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

  The first day of each cycle is denoted Day 1. Therefore, the primary outcome will be the proportion of patients who are clinically fit to start cycle 2 of chemotherapy 14 days later.

  Day 15 of each cycle

Secondary Outcomes (10)

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

  Day 8 and 15

• Plasma methotrexate concentration

  Every 24 hours from Time +24 until clearance of methotrexate

• Incidence of glucarpidase related adverse effects

  6 weeks

• Number of days required in hospital per cycle

  6 weeks

• Assessment of quality of life

  6 weeks

Study Arms (2)

M

ACTIVE COMPARATOR

Methotrexate (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 .

Drug: Methotrexate; Drug: Folinic Acid

GluM

EXPERIMENTAL

Methotrexate (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

Drug: Glucarpidase; Drug: Methotrexate; Drug: Folinic Acid

Interventions

Glucarpidase DRUG

Glucarpidase rescue (50 units/kg x 1, intravenously)

Also known as: Voraxaze

GluM

Methotrexate DRUG

Methotrexate (12 g/m2 x 1, intravenously)

GluM; M

Folinic Acid DRUG

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

GluM; M

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Richard Scowcroft Foundation: collaborator

Study Sites (1)

University College Hospital

London, NW1 2PG, United Kingdom

Location

MeSH Terms

Conditions

Osteosarcoma; Mucositis

Interventions

glucarpidase; Methotrexate; Leucovorin

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes

Study Officials

• Jeremy Whelan, Professor

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 27, 2013
• Study Start: July 1, 2007
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 4, 2015

Record last verified: 2015-06

Locations

GB (1)