Pharmacokinetics of Bendamustine Hydrochloride in Patients With Relapsed or Refractory Malignancy

Open-Label Study to Investigate the Pharmacokinetics of Bendamustine Hydrochloride Following Intravenous Infusion of [14C] Bendamustine Hydrochloride in Patients With Relapsed or Refractory Malignancy

An Open-Label Study to Investigate the Pharmacokinetics of Bendamustine Hydrochloride in Patients With Relapsed or Refractory Malignancy (Hematologic or Nonhematologic)

Study Overview

• Status: Completed
• Conditions: Malignancy
• Intervention / Treatment: Drug: bendamustine

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Please Call For Information

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• The patient must have a histologically or cytologically confirmed, relapsed or refractory malignancy, except for uveal melanoma, sarcoma or primary brain tumors. Additionally, the malignancy must be considered unresponsive or poorly responsive to accepted treatment modalities.
• The patient has a World Health Organization (WHO) performance status of 0-2.
• The patient has an estimated life expectancy of at least 3 months.
• The patient, if a woman, is surgically sterile, 2 years postmenopausal, or, if of child bearing potential, using a medically accepted method of contraception, and agrees to continued use of this method for the duration of the study and for 90 days after discontinuation of study drug. Acceptable methods of contraception include abstinence or an intrauterine device (IUD) known to have a failure rate of less than 1% per year.
• The patient, if a man, is surgically sterile, or, if capable of producing offspring, is currently using an approved method of birth control and agrees to continued use of this method for the duration of the study (and for 90 days after taking the last dose of study medication).
• Absolute neutrophil count (ANC) ≥1000 cells/mm3, platelet count ≥100000 cells/mm3, and hemoglobin greater than or equal to 9 g/dL.
• The patient has adequate hepatic function. For patients without liver metastases, adequate hepatic function is defined as ≤2.5 x upper limit of the normal range [ULN] for aspartate aminotransferase [AST] and alanine aminotransferase [ALT], and ≤1.5 x ULN for total bilirubin. For patients with liver metastases, adequate hepatic function is defined as ≤5 x ULN for AST and ALT, and ≤1.5 x ULN for total bilirubin. Patients with non-clinically significant elevations of bilirubin due to known or suspected Gilbert's disease are eligible; this must be documented on the medical history page of the case report form (CRF).
• The patient has a calculated creatinine clearance of >30 mL/minute as determined by the Cockcroft-Gault equation.

Key Exclusion Criteria:

• The patient has had chemotherapy, radiotherapy, radioimmunotherapy, or immunotherapy within 28 days prior to the first dose of study drug or has not recovered from adverse events due to any agents administered previously. For patients who received therapy with mitomycin C, the interval is 42 days.
• The patient has known cerebral metastases.
• The patient is receiving treatment other than bendamustine for hematologic/nonhematologic malignancy.
• The patient has had any previous treatment with bendamustine.
• The patient has been treated with any hematopoietic growth factors within 14 days of study entry (patients on chronic erythropoiesis stimulating agents are allowed).
• The patient is pregnant or lactating.
• The patient has had a serious infection, medical condition, or psychiatric condition that, in the opinion of the investigator, should preclude the patient from participating in the study.
• The patient has a known positive test result for human immunodeficiency virus (HIV) or a history of HIV disease.
• The patient has presence of inflammatory bowel disease, occlusion of the gastrointestinal tract, significant constipation, or any condition resulting in clinically significant obstruction of the urinary tract.
• The patient requires treatment with cytochrome P450 1A2 (CYP1A2) inducers or inhibitors on days 1 through 8 of cycle 1, has used CYP1A2 inhibitors within 14 days before the 1st administration of study drug, or has used CYP1A2 inducers within 30 days before the 1st administration of study drug.
• The patient is a smoker or an ex-smoker who stopped smoking less than 3 months before the 1st dose of study drug or is using or has used topical or oral nicotine preparations for smoking cessation within the past 3 months before the 1st dose of study drug.
• The patient has known hypersensitivity to bendamustine or any if its components (i.e., mannitol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: bendamustine; Bendamustine 120 mg/m2 on Days 1 and 2 every 28 days (one cycle) for up to 6 cycles. Radiolabeled [14C] bendamustine will be given on day 1 of cycle 1 only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quantitative determination of the pharmacokinetics (distribution, metabolism, and excretion) of [14C]bendamustine and its metabolites in patients with confirmed, relapsed or refractory malignancy.	168 hours (7 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of bendamustine will be assessed throughout the study.	8 months

Collaborators and Investigators

• Sponsor: Cephalon
• Investigators: Study Director: Sponsor's Medical Expert - Sr. Director, Clinical Pharmacology, Cephalon

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Estimate): April 23, 2012
• Last Update Submitted That Met QC Criteria: April 20, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Bendamustine Hydrochloride
• Other Study ID Numbers: C18083/1039/PK/NL