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A Phase II Study of ABT-263/Abiraterone (Arm A) or ABT-263/Abiraterone and Hydroxychloroquine (Arm B) in Patients With Metastatic Castrate Refractory Prostate Cancer (CRPC) and Progression Following Chemotherapy and Abiraterone

Phase 2
18 Years
90 Years
Not Enrolling
Castrate Refractory Prostate Cancer (CRPC)

Thank you

Trial Information

A Phase II Study of ABT-263/Abiraterone (Arm A) or ABT-263/Abiraterone and Hydroxychloroquine (Arm B) in Patients With Metastatic Castrate Refractory Prostate Cancer (CRPC) and Progression Following Chemotherapy and Abiraterone

Subjects will be either treated on one of the earlier dosing regimens or randomly assigned
to one of two groups or ARMs of this study.

ARM A will receive Abiraterone with ABT-263.

ARM B will receive Abiraterone with both ABT-263 and Hydroxychloroquine

In the beginning of the study a total of 18 patients may get one of three dose levels. A
total of nine (9) patients per each arm will be started at a low dose and given increasing
doses if no side effects are seen. In this part of the study three patients will be enrolled
at each dose level for each individual arm starting with Arm A followed by Arm B.

Inclusion Criteria:

- Patients must have had evidence of disease progression while receiving primary
androgen suppression therapy by orchiectomy or other primary hormonal therapy and
abiraterone (Specifically, patients can have received multiple prior additional
androgen axis targeting agents including enzalutamide, and prior chemotherapy, but
must have had progression (as defined in 5.1.2) while receiving abiraterone either
currently or in the past). Patients currently on abiraterone may continue with the
start of the study drug(s).

- Patients must have evidence of disease progression during current or prior therapy
with abiraterone with either:

1. Biochemical progression as defined as rising PSA from a nadir or baseline
(whichever was lowest) confirmed on a second determination at least 1 week later
that must be higher than the first and must have reached ≥2ng/ml (if no other
evidence of progression); or

2. New Metastases on bone scan (at least 2); or

3. Progression of measurable disease on CT scan by RECIST criteria

- Age >18 years and an estimated life expectancy of at least 6 months.

- Treatment with at least 2 months of abiraterone prior to progression

- ECOG performance status ≤ 2. (See Appendix A)

- Patients must be ≥ 4 weeks since completing their prior therapy (including surgery,
radiation therapy or investigational therapy (including targeted small molecule
agents)). All previous clinically significant treatment-related toxicities have
resolved to ≤ Grade 1. Patients must be ≥ 6 weeks since prior therapy with an

- Adequate renal function (serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥50

- Total bilirubin must be within 1.5 X the normal institutional limits. If total
bilirubin is outside the normal institutional limits, assess direct bilirubin. The
direct bilirubin must be within normal parameters. Transaminases (SGOT and/or SGPT)
must be less than 1.5X ULN concomitant with alkaline phosphatase less than 5X the

- An ANC >1500/μl, hemoglobin > 10 g/dl, and platelet count >100,000/mm3 are required.

- Serum testosterone (total) less than 25 ng/ml at time of enrollment.

- Bisphosphonates/RANK-ligand inhibitor allowed if started prior to study treatment

- Patient must consent to using effective contraception while on treatment and for 3
months thereafter

- Subject must voluntarily sign and date an informed consent, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the
initiation of any screening or study-specific procedures

Exclusion Criteria:

- 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

- 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

- 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

- 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

- 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 or hydroxychloroquine

- Known G-6PDH deficiency

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

- Patients presenting with untreated cord compression are not eligible (patients with
prior treatment and stability will be eligible)

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Biochemical response to ABT-263 and Abiraterone and to ABT-263 in combination with Hydroxychloroquine and Abiraterone in patients that are progressing on Abiraterone

Outcome Description:

Characterize "biochemical response" by looking at PSA

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Robert Dipaola, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

April 2013

Completion Date:

April 2016

Related Keywords:

  • Castrate Refractory Prostate Cancer (CRPC)
  • prostate cancer
  • Prostatic Neoplasms



Cancer Institute of New Jersey New Brunswick, New Jersey  08901