Voraxaze for Delayed Methotrexate Clearance

This study has been terminated.
(Sponsor terminated due to low accrual.)
Sponsor:
Collaborator:
BTG International Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00424645
First received: January 17, 2007
Last updated: December 4, 2012
Last verified: December 2012
  Purpose

Primary Objectives:

  1. To evaluate the efficacy of Glucarpidase (Voraxaze) in increasing the rate of methotrexate (MTX) clearance following high dose MTX treatment in patients with a delayed MTX clearance.
  2. To evaluate the pharmacokinetics (PK) of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance.
  3. To evaluate the safety profile of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance.

Secondary Objectives:

  1. To evaluate the effect of Glucarpidase on the incidence of neutropenic fever and use of intravenous (IV) antibiotics.
  2. To evaluate the effect of Glucarpidase on the length of hospitalization.
  3. To evaluate the effect of Glucarpidase on renal function.
  4. To evaluate the effect of Glucarpidase on Quality of Life (QOL).
  5. To evaluate the anti-glucarpidase antibody response.
  6. To evaluate the efficacy of Glucarpidase following its use in repeated cycles of high dose MTX treatment.

Condition Intervention Phase
Hematologic Malignancy
Solid Tumor
Drug: Voraxaze (Glucarpidase)
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Randomized, Double-Blind, Placebo Controlled Trial of Voraxaze™ in Patients With a Delayed MTX Clearance

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Patient Response Rate (Percentage) [ Time Frame: Study period 2 years ] [ Designated as safety issue: Yes ]
    Response rate defined as proportion of patients that clear methotrexate (MTX) at 15 min and 24-hour post infusion of study drug, Glucarpidase (Voraxaze) to total patient number. Serum MTX levels (standard methods and mass spectrometry) at 15 minutes, 24 hours, or daily until MTX clearance defined as serum MTX level <0.1 µmol/L.


Enrollment: 3
Study Start Date: January 2007
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Voraxaze
Voraxaze administered 50 units/kg intravenously (IV) repeated a maximum of 2 times in a given cycle of chemotherapy.
Drug: Voraxaze (Glucarpidase)
50 units/kg IV within 12 hours of study eligibility being confirmed.
Other Name: Carboxypeptidease
Placebo Comparator: Placebo
Placebo administered IV following Voraxaze arm.
Drug: Placebo
Administered by IV within 12 hours of study eligibility being confirmed.

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with solid tumors and hematologic malignancies, receiving high dose methotrexate (MTX) (> / = 1 g/m^2 up to 14 g/m^2), who have delayed MTX clearance. Delayed MTX clearance is defined as: a) Serum MTX level at 72 +/- 2 hrs from initiation of infusion > / = 0.1 µmol/L for MTX doses 1-3.5 g/m^2 OR b) Serum MTX level at 72 +/- 2 hrs from initiation of infusion > / = 0.3 µmol/L for MTX doses > 3.5 g/m^2
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  3. IRB-approved signed informed consent

Exclusion Criteria:

  1. Any medical or psychiatric illness that is deemed by the investigator to be likely to interfere with patient's ability to sign informed consent, cooperate and participate in the study
  2. Patients receiving medications which may interfere with MTX excretion or enhance MTX toxicity (e.g. Penicillins, Cephalosporins, Tetracyclines, Non-Steroidal Anti-inflammatory Agents, Salicylates, Thiazide Diuretics, Bactrim, and Probenecid)
  3. Patients with uncontrolled cardiac disease such as uncontrolled angina, cardiac arrhythmia, or Congestive Heart Failure (CHF) (New York Heart Association (NYHA) 4)
  4. Patients with known hypersensitivity to any of the components of the study drug
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424645

Locations
United States, Texas
U.T. M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
BTG International Inc.
Investigators
Principal Investigator: Saroj Vadhan-Raj, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00424645     History of Changes
Other Study ID Numbers: 2006-0119
Study First Received: January 17, 2007
Results First Received: November 9, 2010
Last Updated: December 4, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Hematologic Malignancy
Solid Tumor
Glucarpidase
Voraxaze
Delayed Methotrexate Clearance
Placebo

Additional relevant MeSH terms:
Neoplasms
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014