A Study to Assess the Effect of Ketoconazole on the Metabolism of ABT-263 (Navitoclax).

A Phase 1 Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of ABT-263 (Navitoclax)

This is a single dose, open-label, single or multiple center study to determine the interaction of ketoconazole with ABT-263 in approximately 12 subjects with cancer.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Chronic Lymphocytic Leukemia; Solid Tumors
• Intervention / Treatment: Drug: ABT-263; Drug: Ketoconazole

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Site Reference ID/Investigator# 25068

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

Inclusion Criteria:

• 18 years of age or older.
• Has a non-hematologic malignancy (radiographic, histologic, or cytologic confirmation), or hematologic malignancy (histologic or cytologic confirmation) that is either: relapsed or refractory to standard therapy, failed at least one prior therapy or no known effective therapy exists.
• In the investigator's opinion, the subject's life expectancy is at least 90 days.
• If clinically indicated, (e.g., subjects over the age of 70) subjects must have documented brain imaging (MRI or CT) negative for subdural or epidural hematoma within 28 days prior to the first dose of study drug.
• Subjects with brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug.

Exclusion Criteria:

• History of or is clinically suspicious for cancer-related central nervous system (CNS) disease.
• Has undergone an allogeneic stem cell transplant.
• Has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding.
• Has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
• Has active immune thrombocytopenic purpura or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).
• Significant history of cardiovascular disease (e.g., MI, thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease. Female subject is pregnant or breast-feeding.
• History of or an active medical condition(s) that affects absorption or motility (e.g., Crohn's disease, celiac disease, gastroparesis, short bowel syndrome, etc).
• Exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: active systemic fungal infection; diagnosis of fever and neutropenia within one week prior to study drug administration.
• Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for hypothyroidism or estrogen replacement therapy [ERT], or agonists required to suppress serum testosterone levels [e.g., LHRH, GnRH, etc.] for subjects with prostate cancer
• Currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function.
• Currently receiving or requires anti-fungal treatment or CYP3A inhibitors. In the opinion of the Investigator, the subject is an unsuitable candidate to receive ABT-263.
• History of or is clinically suspicious for cancer-related central nervous system (CNS) disease.

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: Arm A (ABT-263 and Ketoconozole)	Drug: ABT-263; Subjects will be dosed with ABT-263, then dosed with ABT-263 in combination with Ketoconazole.; Drug: Ketoconazole; Subjects will be dosed with ABT-263, then dosed with ABT-263 in combination with Ketoconazole.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the effect of ketoconazole on the pharmacokinetics of ABT- 263.	Weekly

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the safety of ABT-263 when administered alone and in combination with Ketoconazole in these patients.	Daily

Collaborators and Investigators

• Sponsor: Abbott

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 25, 2009
• First Posted (Estimate): November 30, 2009

Study Record Updates

• Last Update Posted (Estimate): December 20, 2010
• Last Update Submitted That Met QC Criteria: December 16, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole; Navitoclax
• Other Study ID Numbers: M10-957