Advanced Cancer Relapsed Malignancy
Conditions
Interventions
Bendamustine hydrochloride will be administered as an iv infusion over a 60
minute period at a dose of 120 mg/m2 on days 1 and 2 of each treatment cycle.
Bendamustine, containing approximately 90 to
Sponsors
Cephalon Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: (a) The patient must have a histologically or cytologically confirmed, relapsed or refractory malignancy (hematologic or nonhematologic) except for uveal melanoma, sarcoma or primary brain tumors. Additionally, the malignancy must be considered unresponsive or poorly responsive to accepted treatment modalities. (b) The patient has a WHO performance status of 0-2. (c) The patient has an estimated life expectancy of at least 3 months. (d) Written informed consent is obtained. (e) The patient is at least 18 years of age at the time of informed consent. (f) NOTE: This inclusion criterion is no longer effective with the implementation of amendment 3; it is replaced by inclusion criterion (k): The patient, if a woman, is surgically sterile or 2 years postmenopausal. (g) 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 due to possible effects on spermatogenesis). Acceptable methods of contraception include abstinence, surgically sterile, female partner*s use of steroidal contraceptive in conjunction with a barrier method, female partner*s use of an intrauterine device (known to have a failure rate of less than 1% per year), or female partner is surgically sterile for 2 years or more, or is 2 years postmenopausal. In addition, men may not donate sperm for the duration of the study (and for 90 days after taking the last dose of study medication). (h) ANC >=1000 cells/mm3, platelet count >=100000 cells/mm3 and hemoglobin greater than or equal to 9 g/dL. (i) The patient has adequate hepatic function. For patients without liver metastases, adequate hepatic function is defined as 30 mL/minute as determined by the Cockroft-Gault equation. (k) The patient, if a woman, must be surgically sterile, 2 years postmenopausal, or, if of child-bearing potential, using a medically accepted method of contraception, and agree 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. NOTE: This inclusion criterion replaces inclusion criterion (f) and is effective with the implementation of amendment 3.
Exclusion criteria
Exclusion criteria: (a) 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. (b) The patient has known cerebral metastases. (c) The patient is receiving treatment other than bendamustine for hematologic/nonhematologic malignancy. (d) The patient has had any previous treatment with bendamustine. (e) The patient has been treated with any hematopoietic growth factors within 14 days of study entry (patients on chronic erythropoiesis stimulating agents are allowed). (f) The patient is pregnant or lactating. (g) 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. (h) The patient has a known positive test result for human immunodeficiency virus (HIV) or a history of HIV disease. (i) 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. (j) 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. (k) NOTE: This exclusion criterion is no longer effective with the implementation of amendment 3; it is replaced by inclusion criterion (m): The patient is a smoker or an ex-smoker who stopped smoking less than 12 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. (l) The patient has known hypersensitivity to bendamustine or any if its components (ie, mannitol). (m) 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. NOTE: This exclusion criterion replaces inclusion criterion (k) and is effective with the implementation of amendment 3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Prior to the start of study drug administration and at prespecified time points through 168 hours after the start of study drug administration on day 1 of cycle 1, blood, urine, and fecal samples will be collected to evaluate the distribution, metabolism, and excretion of [14C]bendamustine. Analysis of the blood and plasma samples for total radioactivity (TRA) will be done by liquid scintillation counting (LSC). Plasma concentrations of bendamustine and its metabolites γ hydroxy-bendamustine (M3), N-desmethyl-bendamustine (M4), monohydroxybendamustine (HP1), and dihydroxybendamustine (HP2) will be determined using a validated high performance liquid chromatography (HPLC) method with tandem mass spectrometric detection (LC MS/MS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety measures and endpoints will include the following: • occurrence of adverse events and concomitant medication usage throughout the study • clinical laboratory (hematology, serum chemistry, and/or urinalysis) • vital signs and body weight measurements • 12 lead ECG findings at specified time points • physical examination findings | — |
Countries
Netherlands
Outcome results
None listed