An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib)

January 26, 2012 updated by: Millennium Pharmaceuticals, Inc.
The primary purpose of this Phase I study is to evaluate the effect of the co-administration of CYP3A4 inducers on the pharmacokinetics profile of VELCADE (bortezomib). Rifampicin will be used to assess the effect of a strong CYP3A4 inducer and dexamethasone to assess the effect of a relatively weak inducer. This study is also to evaluate the impact of CYP3A4 inducers on the pharmacodynamics (PD) of VELCADE and the safety profile of VELCADE.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Petach Tikva, Israel, 49100
        • Hematology Institute - Davidoff Center - Rabin Medical Center
  • Italy
      • Rome, Italy, 10001
        • Divisione di Ematologia - Ospedale S Eugenio - P. le dell'Umanesimo
  • Poland
      • Gdansk, Poland, 80-952
        • Medical Academy - Dept of Hematology and Transplantology
      • Warszawa, Poland, 02-781
        • Klinika Nowotworow Ukladu - Chlonnego - Centrum Onkologii - Instytut
  • South Africa
      • Bloemfontein, South Africa, 9300
        • Department of Hematology - University of the Free State
      • Pretoria, South Africa, 0001
        • Department of Medical Oncology - Ward 51 - Pretoria Academic Hospital
    • Cape Town
      • Parow, Cape Town, South Africa
        • Hematological Oncology
  • United Kingdom
      • Plymouth, United Kingdom, PL6 8DH
        • Hematology Department Combined Laboratories - Derriford Hospital
    • Plymouth
      • Derriford, Plymouth, United Kingdom, PL68DH
        • Plymouth Hospitals NHS Trust - Derriford Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female of at least 18 years of age.
  • Has documented relapsed or refractory multiple myeloma or NHL following prior anti-neoplastic treatment.
  • Female patients must be post menopausal for at least 1 year (must not have had a natural menses for at least 12 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; have a negative serum β-HCG or a negative urine pregnancy test at screening. (an alternative to oral contraceptives should be used if the patient is randomized to Arm B with rifampicin).
  • Male patients must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study.
  • Must be able to swallow capsules/tablets whole (without chewing, crushing, or opening).
  • Agree to refrain from the use of any methylxanthine-containing products, including caffeine (e.g., chocolate bars or beverages, coffee, teas, or colas), on Day 11 of Cycles 2 and 3.
  • Agree to refrain from the use of any products containing nicotine, alcohol, quinine, grapefruit juice, or Seville oranges from 7 days before the first administration of VELCADE through completion of the 72-hour PK blood sample collection (post Day 11 VELCADE dose) in Cycle 3.

Exclusion Criteria:

  • Diagnosis or treatment of a malignancy other than multiple myeloma or NHL within 1 year of randomization, or who have previously been diagnosed with a malignancy other than multiple myeloma or NHL and have any radiographic or biochemical marker evidence of malignancy.
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbances.
  • Known or suspected hypersensitivity or intolerance to rifampicin and/or other antibiotics, corticosteroids, boron or mannitol.
  • Peripheral neuropathy or neuropathic pain Grade 2 or higher.
  • Preplanned surgery or procedures that would interfere with the conduct of the study or major surgery within 2 weeks before randomization.

  • History of disallowed therapies:

    • Prior treatment with VELCADE.
    • Any drugs or agents that inhibit (e.g., cimetidine, erythromycin, fluoxetine, ketoconazole, paroxetine) or induce (e.g., carbamazepine, glucocorticoids, phenobarbital, phenytoin, St. John's Wort) CYP2C19 or CYP3A4 within 28 days before the first administration of VELCADE.
    • Any exposure to rifampicin or corticosteroids within 28 days of screening.
    • Have received an investigational agent or used an investigational medical device within 28 days before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
  • Female patient who is pregnant or breastfeeding.
  • Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VELCADE
Control arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle.
Drug: bortezomib
1.3 mg/m^3 on days 1, 4, 8, 11 over a 21-day treatment cycle
Other Names:
  • VELCADE
Experimental: VELCADE + rifampicin
Treatment Arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3.
Drug: bortezomib, rifampicin
bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3
Other Names:
  • bortezomib
  • rifampicin
Experimental: VELCADE + dexamethasone
Treatment arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3.
Drug: bortezomib, dexamethasone
bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3
Other Names:
  • dexamethasone
  • bortezomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours
Time Frame: Cycle 3 day 14 (72 hours post last dose)
Cycle 3 day 14 (72 hours post last dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Millennium Pharmaceuticals, Inc.

Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

January 23, 2008

First Submitted That Met QC Criteria

January 23, 2008

First Posted (Estimate)

February 6, 2008

Study Record Updates

Last Update Posted (Estimate)

January 30, 2012

Last Update Submitted That Met QC Criteria

January 26, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 26866138-CAN-1006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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