Comparison of Pharmacokinetics and Pharmacodynamics of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by:
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT00291538
First received: February 10, 2006
Last updated: February 3, 2009
Last verified: February 2009
  Purpose

In this open-label randomised phase I trial, bortezomib will be administrated to 2 groups of 10 patients with MM who have inclusion criteria use the extended 2nd line indication, either intravenously (group 1 = 10 patients) or subcutaneously (group 2 = 10 patients). The schedule of administration of bortezomib will be the following : 1.3 mg per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles, either IV (group 1) or SC (group 2).

The primary objective is to characterize the pharmacokinetics of the 2 routes of administration.

The secondary objectives are to characterize the pharmacodynamics (20S proteasome inhibition in whole blood), toxicity, including cardiac safety, and efficacy of the 2 routes of administration.


Condition Intervention Phase
Multiple Myeloma
Drug: bortezomib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Pharmacokinetics and Pharmacodynamics of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • characterize the pharmacokinetics of the 2 routes of administration.

Secondary Outcome Measures:
  • characterize the pharmacodynamics (20S proteasome inhibition in whole blood),
  • toxicity, including cardiac safety,
  • efficacy of the 2 routes of administration.

Estimated Enrollment: 20
Study Start Date: February 2006
Study Completion Date: October 2008
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of MM according to the SWOG criteria (annex I)
  • symptomatic MM stage II or III according to Durie-Salmon staging system (annex II) or stage I with one symptomatic osteolytic lesion
  • with progressive disease after at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation
  • with measurable levels of paraprotein in the serum (> 1g/dl) or in the urine (> 0.2g/24h)
  • age < 75 years
  • able to understand and to given an informed consent
  • male, female without childbearing potential or negative urine pregnancy test within 72 hours prior to beginning the treatment. Women of childbearing potential must be following adequate contraceptive measures. Men must agree to use an acceptable method of contraception (for themselves or female partners) for the duration of the study
  • no active systemic infection. In the presence of any active systemic infection, adequate broad-spectrum or organism-specific antibiotic coverage must be administered. Patients must be afebrile with stable vital signs while receiving antibiotics for at least 48 hours prior to beginning the treatment with Bortezomib.
  • Each subject will weigh ³50 kg and have a body mass index (BMI) of £30 kg/m2 (see annex V for BMI formula).

Exclusion Criteria:

  • life expectancy < 2 months
  • ECOG performance status > 2 (annex III)
  • proven amyloidosis
  • positive HIV serology
  • antecedents of severe psychiatric disease
  • > NCI grade 2 peripheral neuropathy (Annex IV)
  • History of clinically relevant cardiac disease, including prior myocardial infarction, prior or existing heart failure, existing uncontrolled angina or clinically significant pericardial disease Evidence of arrhythmia, 2nd degree or greater AV block or prolonged QTc interval (>0.45 seconds in males, >0.47 seconds in females) on screening ECG
  • serum biochemical values as follow
  • creatinine level > 200mmol/l
  • bilirubin, transaminases or gGT > 3 the upper normal limit
  • potassium, calcium or magnesium outside of upper or lower normal limits
  • haematology values as follow
  • platelet < 70x 109 /L within 14 days of enrollment
  • absolute neutrophil count <1.0 x 109/L within 14 days of enrolment
  • concomitant use of drugs able to modify QTc interval within 1 week prior to the first dose of bortezomib and during Cycle 1 (Annex VI)
  • concomitant use of potent inhibitors or inducers of the cytochrome P450 (CYP) enzymes 3A and 2C19 within 1 week prior to the first dose of bortezomib and during Cycle 1 (see annex VII list of representative drugs).
  • use of any experimental drugs within 30 days of baseline
  • hypersensitivity to bortezomib, boron, or mannitol
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00291538

Locations
France
Lille UH
Lille, France, 59000
Nancy UH
Nancy, France, 54000
Nantes UH
Nantes, France, 44093
Sponsors and Collaborators
Nantes University Hospital
Investigators
Principal Investigator: Jean-Luc HAROUSSEAU, MD Nantes UH
  More Information

No publications provided by Nantes University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00291538     History of Changes
Other Study ID Numbers: BRD/05/9-B
Study First Received: February 10, 2006
Last Updated: February 3, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014