Navitoclax and Abiraterone Acetate With or Without Hydroxychloroquine in Treating Patients With Progressive Metastatic Castrate Refractory Prostate Cancer

Known infection with HIV or subject has tested positive for HIV (due to potential drug-drug interactions between anti-retroviral inhibitors and ABT-263, as well as anticipated ABT-263 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain anti infective agents). Patients without prior HIV testing will not be required to be tested.

Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence.

Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

* active systemic fungal infection;

* diagnosis of fever and neutropenia within 1 week prior to study drug administration

Patients must discontinue all herbal supplements at a minimum of one week prior to initiation of therapy (such information will be collected on each patient

Requirement for routine use of hematopoietic growth factors (including granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, or interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or platelets counts above the required thresholds for study entry.

Patient has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. The subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within 1 year prior to the first dose of study drug.

History or symptoms of cardiovascular disease (NYHA Class 2, 3, or 4; see Appendix B, New York Heart Association Criteria) within the last 6 months, particularly coronary artery disease, arrhythmias, or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, or congestive heart failure.

Hypersensitivity to 4-aminoquinoline compounds, including hydroxychloroquine sulfate, chloroquine phosphate and amodiaquine.

Prior history of treatment with ABT-263

Known G-6PDH deficiency

Retinal or visual field changes from prior 4-aminoquinoline compound use such as hydroxychloroquine sulfate, chloroquine phosphate and amodiaquine.

Concurrent use of other investigational agent

Subject has undergone an allogeneic stem cell transplant

Subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis

Subject has a 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 that in the opinion of the Investigator would adversely affect his/her participating in this study. Subject has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.

Subject is currently receiving or requires anticoagulation therapy (e.g., warfarin at any dose) or any drugs (e.g., aspirin, clopidogrel, etc) or herbal supplements that affect platelet function, with the exception of low molecular weight heparin or heparin that are used to maintain the patency of a catheter.

Subject has received aspirin or warfarin within 7 days prior to the first dose of study drug.

Subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.

Received potent CYP3A inhibitors (e.g., ketoconazole) or inducers (substrates of CYP2D6) within 7 days prior to the first dose of study drug.

Subject has received rifampin within 4 days prior to first dose of ABT-263

What this study is about