advanced solid tumors malignant conditions of the blood relapsed and/or refractory hematologic malignancies solid lumps.
Conditions
Interventions
Study Drug Dose, Mode of Administration, and Administration Rate:
For period A, a single 1.25 mg/m2 sc dose of omacetaxine radiolabeled with
approximately 95 µCi of 14C will be administered at the
Sponsors
TEVA Pharma
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: (a) Written informed consent is obtained. (b) The patient is at least 18 years of age at the time of informed consent. (c) The patient has a histologically or cytologically confirmed diagnosis of: - Relapsed or refractory leukemia, including Philedelphia chromosome-positive (Ph+), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), acute myelogenous leukemia (AML), or myelodysplastic syndrome (MDS). - Advanced solid tumors (ie, breast, lung, head/neck, colorectal, melanoma, and sarcoma). The malignancy must be considered unresponsive to accepted available therapies. (d) The patient has an estimated life expectancy of at least 3 months. (e) The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ULN for AST and 1.0-1.5xULN for total bilirubin. Patients with nonclinically significant elevations of bilirubin up to 5.0 g/dL (85500 µmol/L) due to known or suspected Gilbert*s disease are eligible; this must be documented on the medical history page of the CRF. (j) The patient has adequate renal function (normal to mild dysfunction), with a calculated creatinine clearance (CLCR) of >=60 mL/minute (>=1.0 mL/s), as determined by the Cockroft-Gault equation. (k) The patient must be willing and able to comply with study restrictions and to remain at the study center for the required duration during assessment period A.;Patients with non-hematologic malignancies (l) The patient has an absolute neutrophil count (ANC) of >=1000 cells/mm3, a platelet count >=100000 cells/mm3, and a hemoglobin value >=8 g/dL.;Patients with hematologic malignancies (m) The patient has a hemoglobin value which is, in the opinion of the investigator, adequate given the blood draw requirements of the study.
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 is receiving any other treatment for hematologic/nonhematologic malignancy. (c) The patient has had previous treatment with omacetaxine mepesuccinate. (d) The patient has been treated with any hematopoietic growth factors within 14 days of study entry (patients on chronic erythropoiesis stimulating agents are allowed). (e) The patient has New York Heart Association (NYHA) Class 3 or 4 heart disease, active ischemia, or any uncontrolled, unstable cardiac condition for which treatment for the condition is indicated but is not controlled despite adequate therapy, including angina pectoris, cardiac arrhythmia, hypertension, or congestive heart failure. (f) The patient has experienced a myocardial infarction within the previous 12 weeks. (g) The patient has a solid tumor with symptomatic central nervous system (CNS) metastases. (h) The patient has an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment. (i) The patient is pregnant or lactating. (j) The patient has had a serious medical or psychiatric condition that, in the opinion of the investigator, should preclude the patient from participating in the study. (k)The patient has * a positive test result for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C (serology tests for HBsAg and hepatitis C antibodies must be negative), and/or * a known positive test result for human immunodeficiency virus (HIV) or a history of HIV disease (if HIV status is unknown it is assumed that it is negative). (l) 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 gastrointestinal tract. (m) The patient has any condition resulting in a clinically significant obstruction of the urinary tract. (n) The patient has known hypersensitivity to omacetaxine mepesuccinate, mannitol, or any other components of the study drug. (o) The patient is considered unsuitable for any other reason, as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: The primary objective of the study is to quantitatively determine the pharmacokinetics (absorption, distribution, metabolism, and excretion) of [14C]omacetaxine mepesuccinate and its metabolites in patients with relapsed and/or refractory hematologic malignancies or advanced solid tumors. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Variables and Endpoints: Blood samples (6 mL at each time point) will be collected (via venipuncture or indwelling catheter) prior to administration of the radiolabeled dose of omacetaxine and 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 32, 48, and 72 hours after administration of the radiolabeled dose of omacetaxine. Omacetaxine, 4'-DMHHT, and cephalotaxine will be qualified for all plasma samples obtained trhough 72 hours after administration of the radiolabeled dose of omacetaxine on day 1 of period A.The following pharmacokinetic parameters of the radiolabeled dose of omacetaxine on day 1 of period A. - maximum observed plasma drug concentration (Cmax) by inspection (without interpolation) - time to maximum observed plasma drug concentration, by inspection (tmax) - area under the plasma concentration by time curve (AUC) from time 0 to infinity (AUC0-*) - AUC from time 0 to the time of the last measurable drug concentration (AUC0-t) - terminal rate constant (*z) and associated terminal half-life (t*) - percentage extrapolation calculated as (AUC0-*-AUC0-t)/(AUC0-*)x100 - apparent plasma clearance (CL/F) - apparent volume of distribution (Vz/F) For 4*-DMHHT, and cephalotaxine, Cmax by inspection (without interpolation), tmax, AUC0 t, *z, and t* will be calculated, if possible. Blood samples (4 mL each) will be obtained 96, 120, 144 and 168 hours after administration of the radiolabeled dose of omacetaxine. An additional 1 mL blood sample will be collected 30 minutes and 8, 72, and 168 hours after administration of the radiolabeled dose of omacetaxine for determination of TRA to enable calculation of the blood:plasma ratio. If quantifiable levels of radioactivity remains at 168 hours, a 1 mL blood sample may also be collected on an outpatient (twice-a weekly) basis to enable monitoring of the kinetics of residual radioactivity. Plasma: blood ratios of concentrations of radioactivity will also be calculated. A single | — |
Countries
Netherlands
Outcome results
None listed