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

NCT ID: NCT00608907

Last Updated: 2012-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-04-30

Brief Summary

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.

Conditions

Multiple Myeloma; Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VELCADE

Control arm, bortezomib 1.3 mg/m\^2 on days 1, 4, 8, 11 over a 21-day treatment cycle.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

1.3 mg/m\^3 on days 1, 4, 8, 11 over a 21-day treatment cycle

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.

Group Type: EXPERIMENTAL

bortezomib, rifampicin

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

bortezomib, dexamethasone

Intervention Type: DRUG

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

Interventions

bortezomib

1.3 mg/m\^3 on days 1, 4, 8, 11 over a 21-day treatment cycle

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

VELCADE; bortezomib; rifampicin; bortezomib; dexamethasone

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Hematology Institute - Davidoff Center - Rabin Medical Center

Petah Tikva, , Israel

Divisione di Ematologia - Ospedale S Eugenio - P. le dell'Umanesimo

Rome, , Italy

Medical Academy - Dept of Hematology and Transplantology

Gdansk, , Poland

Klinika Nowotworow Ukladu - Chlonnego - Centrum Onkologii - Instytut

Warsaw, , Poland

Hematological Oncology

Parow, Cape Town, South Africa

Department of Hematology - University of the Free State

Bloemfontein, , South Africa

Department of Medical Oncology - Ward 51 - Pretoria Academic Hospital

Pretoria, , South Africa

Plymouth Hospitals NHS Trust - Derriford Hospital

Derriford, Plymouth, United Kingdom

Hematology Department Combined Laboratories - Derriford Hospital

Plymouth, , United Kingdom

Countries

Israel; Italy; Poland; South Africa; United Kingdom

Other Identifiers

26866138-CAN-1006

Identifier Type: -

Identifier Source: org_study_id