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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00291538
• Other study ID #: BRD/05/9-B
• Status: Completed
• Phase: Phase 1
• First received: February 10, 2006
• Last updated: February 3, 2009
• Start date: February 2006
• Est. completion date: October 2008

Study information

• Verified date: February 2009
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2008
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• bortezomib

Locations

Country	Name	City	State
France	Lille UH	Lille
France	Nancy UH	Nancy
France	Nantes UH	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	characterize the pharmacokinetics of the 2 routes of administration.
Secondary	characterize the pharmacodynamics (20S proteasome inhibition in whole blood),
Secondary	toxicity, including cardiac safety,
Secondary	efficacy of the 2 routes of administration.