Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function
Information source: Celgene Corporation
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: MDS; AML; Solid Tumors; Multiple Myeloma; Non-Hodgkin's Lymphoma; Hodgkin's Disease
Intervention: azacitidine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Celgene Corporation Official(s) and/or principal investigator(s): CL Beach, PharmD, Study Director, Affiliation: Celgene Corporation
Summary
The primary study objectives were:
- to assess the dose proportionality of azacitidine pharmacokinetics (PK) after single
subcutaneous (SC) doses of the drug ranging from 25 to 100 mg/m^2 (Part 1)
- to determine the effect of renal impairment on azacitidine PK after single and multiple
(5 days) SC doses of 75mg/m^2 azacitidine (Part 2)
- to assess the safety and tolerability of azacitidine given SC in cancer patients with
normal renal function (Part 1) and in patients with varying degrees of renal impairment
(Part 2).
Clinical Details
Official title: A Phase 1, Open-Label, Multi-Center, Parallel Group Study to the Pharmacokinetics and Safety of Subcutaneous Azacitidine in Adult Cancer Patients With and Without Impaired Renal Function
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label
Primary outcome: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-doseArea Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Area Under the Plasma Concentration-time Curve From Time Zero to Infinity Maximum Plasma Concentration of Azacitidine (Cmax) Time to Maximum Plasma Concentration of Azacitidine (Tmax) Terminal Phase Half-life of Azacitidine (t½) Apparent Total Clearance of Azacitidine (CL/F) Apparent Volume of Distribution of Azacitidine (Vz/F) Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose After Single and Multiple Doses of Azacitidine Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Time Point After Single and Multiple Doses of Azacitidine Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine Maximum Plasma Concentration of Azacitidine (Cmax) After Single and Multiple Doses of Azacitidine Time to Maximum Plasma Concentration of Azacitidine (Tmax) After Single and Multiple Doses of Azacitidine Terminal Phase Half-life of Azacitidine (t½) After Single and Multiple Doses of Azacitidine Apparent Total Clearance of Azacitidine (CL/F) After Single and Multiple Doses of Azacitidine Apparent Volume of Distribution of Azacitidine (Vz/F) After Single and Multiple Doses of Azacitidine Number of Participants With Adverse Events (AEs)
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Diagnosis of one of the following:
- Myelodysplastic syndromes (MDS) according to the French-American-British (FAB)
classification system: refractory anemia (RA), refractory anemia with ringed
sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory
anemia with excess blasts in transformation (RAEB-T), or chronic myelomonocytic
leukemia (CMML); or
- Acute myelogenous leukemia (AML) in remission,
- Malignant solid tumor,
- Multiple myeloma (MM),
- Non-Hodgkin lymphoma (NHL), or
- Hodgkin lymphoma (HD)
- Solid tumor patients with metastatic (except hepatic) or inoperable solid tumors for
which no standard treatment existed, or had progressed or recurred following prior
therapy. The lack of eligibility for therapy of higher curative potential (where an
alternative therapy has been shown to prolong survival in an analogous population).
- Patients with a history of treated brain metastases should be clinically stable for
greater than 4 weeks prior to signing the informed consent form and off
glucocorticoid therapy for central nervous system (CNS) edema for at least 4 weeks.
- Be capable of giving informed consent
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Have a life expectancy ≥ 3 months
- Have stable renal function for at least 2 months
- Have average calculated creatinine clearance of:
- >80 mL/min/1. 73m^2 for Cohorts 1, 2, 3, and 4
- <30 mL/min/1. 73m^2 for Cohort 5 - Severe renal impairment,
- 50-80 mL/min/1. 73m^2 for Cohort 6 - Mild renal impairment,
- 30 to <50 mL/min/1. 73m^2 for Cohort 7 - Moderate renal impairment
- Have organ and marrow function at the screening and pre-dose visits as defined below:
- Hemoglobin ≥8 g/dL,
- Absolute neutrophil count ≥0. 75 x 10^3/µL,
- Platelets ≥30 x 10^3/µL,
- Total bilirubin ≤1. 5 times the upper limit of normal (ULN),
- Aspartate aminotransferase (AST) ≤2 times the ULN, and
- Alanine transaminase (ALT) ≤2 times the ULN;
- Have a 12-lead electrocardiogram (ECG) that is not clinically significant, as
determined by the Investigator, at screening
- Have serum bicarbonate:
- ≥20 milliequivalents (mEq)/L for patients with normal renal function (cohorts 1,
2, 3 and 4),
- ≥16 mEq/L for patients with impaired renal function (cohorts 5, 6 and 7)
- Women of childbearing potential may participate, providing are not pregnant and agree
to use at least 2 effective contraceptive methods throughout the study.
- Males with a female partner of childbearing potential must agree to use at least 2
effective contraceptive methods throughout the study.
- Be a nonsmoker or must not have smoked for at least 30 days before the screening
visit and agree to abstain from smoking during study participation.
Exclusion Criteria:
- Women who are pregnant or nursing.
- Had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to Day 1.
- Have been treated with an investigational agent within 4 weeks prior to Day 1.
- Have ongoing clinically significant adverse event(s) due to chemotherapy,
radiotherapy or investigational agents administered more than 4 weeks prior to Day 1
as determined by the Investigator.
- Have known or suspected hypersensitivity to azacitidine or mannitol.
- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia.
- Have low blood pressure (supine blood pressure <90/60 mmHg).
- Have human immunodeficiency virus (HIV), or active hepatitis virus B or C.
- Have advanced malignant hepatic tumors.
- Have end stage renal disease requiring dialysis.
- Have psychiatric illness or alcohol/chemical abuse, which could have prevented
granting of informed consent.
- Have advanced malignant hepatic tumors.
Locations and Contacts
Sutter East Bay Hospitals, Berkley, California 94704, United States
Palm Springs Research Institute, Hialeah, Florida 33012, United States
MCG Cancer Center, Augusta, Georgia 30912, United States
Joliet Oncology-Hematology Associates, Ltd., Joliet, Illinois 60435, United States
University of Kentucky-Markey Cancer Center Clinical Research Organization, Lexington, Kentucky 40536, United States
Nevada Cancer Institute, Las Vegas, Nevada 89135, United States
Montefiore Medical Center, Bronx, New York 10461, United States
Mid Dakota Clinical P.C. - Cancer Treatment and Research Center, Bismarck, North Dakota 58501, United States
Gabrail Cancer Center, Canton, Ohio 44718, United States
Pharma Resource, East Providence, Rhode Island 02915, United States
Cancer Therapy and Research Center, San Antonio, Texas 78229, United States
Additional Information
Starting date: November 2008
Last updated: August 2, 2013
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