Safety Profile, MTD, and PK Profile Studies of ABT-263 When Administered in Combination With Standard and Weekly Regimens of Docetaxel in Subjects With Cancer

Exclusion Criteria

• •The subject has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. The subject has a recent history of thrombocytopenia associated with bleeding within 1 year prior to first dose of study drug.
• •The subject is currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications (i.e., Heparin) that are used to maintain the patency of a central intravenous catheter.
• •A female subject is pregnant or breast-feeding.
• •The subject has active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.
• •The subject has active immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).
• •The subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal therapy (with the exception of hormones for hypothyroidism, estrogen replacement therapy \[ERT\], anti estrogen analogs, agonists required to suppress serum testosterone levels \[e.g., LHRH, GnRH, etc.\] for subjects with prostate cancer if on a stable dose for at least 21 days prior to the first dose of study drug), or any investigational therapy with 14 days prior to the first dose of study drug, or has not recovered to less than a grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy.
• •The subject has received an antibody therapy or other biologic (with the exception of colony stimulating factors \[G-CSF, GM-CSF\] or erythropoietin) within 28 days prior to the first dose of study drug.
• •The subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.
• •The subject has received steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug with the exception of inhaled steroids for asthma, topical steroids, replacement/stress corticosteroids, or corticosteroids taken as premedication for this study.
• •The subject has received aspirin or known CYP3A inhibitor (e.g., ketoconazole) within 7 days prior to the first dose of study drug.
• •The subject has undergone an allogeneic stem cell transplant.
• •The subject has received radio-immunotherapy within 6 months prior to the first dose of study drug.
• •The subject has a history of hypersensitivity to docetaxel or other polysorbate 80 drugs.
• •The subject has tested positive for human immunodeficiency virus, HIV (due to potential drug-drug interactions between anti-retroviral medications and navitoclax (ABT-263), as well as anticipated navitoclax (ABT-263) mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain anti infective agents).
• •The subject has a significant history of cardiovascular (e.g., MI, thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study. Questions regarding inclusion of individual subjects should be directed to the Abbott Medical Monitor or designee.
• •The subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• •* active systemic fungal infection;
• •* A diagnosis of fever and neutropenia within 1 week prior to study drug administration.