Gene Expression in Patients With Metastatic Prostate Cancer Receiving CYP-17 Inhibition Therapy

PRIMARY OBJECTIVES:

I. To determine whether somatic tumor genome alterations identified in tumor tissue before or
after the initiation of CYP-17 inhibition with abiraterone acetate therapy are associated
with a 12-week composite progression free survival (PFS) endpoint.

II. To use tumor tissue obtained prior to the initiation of therapy and from the 12 week
biopsy to develop tumor xenografts for mechanistic and functional studies which will
determine whether mutations identified in the tumor genome are associated with response to
drugs that target the observed mutated genes and/or associated pathways.

SECONDARY OBJECTIVES:

I. To determine whether somatic tumor genome alterations identified before or after
initiating CYP-17 inhibition with abiraterone acetate therapy are associated with overall
survival.

II. To determine whether somatic tumor genome alterations identified in tumor tissue before
or after the initiation of CYP-17 inhibition with abiraterone acetate therapy are associated
with progression free survival (PFS).

III. To evaluate circulatory markers in blood and urine specimens for response and/or
resistance to treatment. (Exploratory and correlative objectives)

OUTLINE:

Tissue, blood, and urine samples are collected at baseline and after 12-14 weeks of treatment
and assessed for circulating tumor cells, genome-wide single-nucleotide polymorphism (SNP),
and exome sequencing.

Inclusion Criteria:

- Histological diagnosis of adenocarcinoma of the prostate or documented history in
medical records of having received treatment for prostate cancer diagnosis

- Metastatic disease on chest, abdominal, or pelvic computed tomography (CT) and/or bone
scan amenable to biopsy

- Hemoglobin (HgB) > 9.0 gm

- Absolute neutrophil count (ANC) >= 1500 cells/L

- Platelets >= 100,000 u/L

- Creatinine =< 1.5 x upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) and
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase (ALT)) =< 1.5 x
ULN

- Castrate serum testosterone level (< 50 ng/dL -or- < 1.7 nmol/L)

- Progression while on or after androgen deprivation therapy defined as:

- Progressive measurable disease: at least a 20% increase in the sum of the longest
diameters of measurable lesions over the smallest sum observed or the appearance
of one or more new lesions as assessed by imaging during hormone ablation
treatment; measurable lesions are nodal or visceral soft-tissue lesions with
nodal lesions >= 20 mm in diameter or visceral/soft-tissue lesions >= 10 mm in
diameter OR

- Bone scan progression: appearance of 2 or more new lesions on bone scan during
hormone ablation treatment OR

- Increasing serum prostate-specific antigen (PSA) level: two consecutive increases
in PSA levels documented over a previous reference value obtained at least one
week apart are required; if the third PSA value is less than the second, an
additional fourth test to confirm a rising PSA is acceptable; a minimum starting
value of 2.0 ng/mL is required for study enrollment

- Note: androgen deprivation therapy may have included either medical or surgical
castration

- >= 14 days has passed since completing radiotherapy (exception for radiotherapy: >= 7
days since completing a single fraction of =< 800 centigray (cGy) to a restricted
field or limited-field radiotherapy to non-marrow bearing area such as an extremity or
orbit) at the time of registration

- Patients who may have received systemic chemotherapy or any novel therapeutic CYP-17
inhibitor and/or novel androgen receptor (AR) inhibitor agents previously for prostate
cancer should have received the last dose of the previously administered systemic
therapy >= 12 months from the date of registration

- Provide informed written consent

- Has recovered from any other therapy-related toxicity to =< grade 2, (except alopecia,
anemia and any signs or symptoms of androgen deprivation therapy)

- Willing to provide tissue and blood samples for correlative research purposes

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Patient is considered a candidate for initiating CYP-17 inhibitors abiraterone acetate
and prednisone after failure of hormonal therapy and has no contra-indication to
starting this combination as standard of care

- Patients have stopped any antiandrogen therapy (including bicalutamide) >= 4 weeks
prior to first dose of study drug; in addition any other therapies for prostate
cancer, other than gonadotropin-releasing hormone (GnRH) analogue therapy, such as
progesterone, medroxyprogesterone, progestins (megestrol), or 5-alpha reductase
inhibitors (e.g., finasteride or dutasteride), must be discontinued >= 2 weeks before
the first dose of study drug

Exclusion Criteria:

- Use of any of these therapies =< 12 months prior to registration:

- Use of any of the standard therapies for castrate resistant prostate cancer
(CRPC) stage =< 12 months prior to registration; Note: see below for further
exclusion details of specific standard therapies

- Initiation of full dose chemotherapy with docetaxel for CRPC stage =< 12
months prior to registration is an exclusion criterion

- Note: docetaxel for hormone sensitive prostate cancer is not an
exclusion criterion

- Use of radium-223 for CRPC stage is an exclusion criteria

- Use of Provenge vaccine for CRPC =< 12 months prior to registration is an
exclusion criterion

- Note: less than 3 doses of Provenge vaccine =< 12 months prior to
registration for CRPC is not an exclusion criterion

- Initiation of full dose chemotherapy with mitoxantrone for CRPC stage
with-in the previous 12 months is an exclusion criterion

- Use of cabazitaxel chemotherapy =< 12 months prior to registration is an
exclusion criterion

- Note: initiation of full dose chemotherapy with cabazitaxel for CRPC
stage with-in the previous 12 months is an exclusion criterion

- Use of ketoconazole with steroids =< 12 months prior to registration for
CRPC stage

- Note: ketoconazole therapy taken for a time period of =< 12 weeks in
the 12 month period prior to registration is not an exclusion criterion

- Use of enzalutamide for CRPC stage =< 12 months prior to registration is an
exclusion criteria use of any experimental or standard of care CYP-17
inhibitors =< 12 months prior to registration is an exclusion criteria

- Note: standard of care CRPC therapy with a CYP-17 inhibitor =< 7 days
prior to registration is not an exclusion criterion; if taken for 8
days or more it will be counted as an exclusion criterion

- Receiving any intermittent hormonal treatment GnRH analogues and has not yet achieved
sub-castrate levels of testosterone (< 50 ng/dl or < 1.7 mmol/L)

- History of or current documented brain metastasis or carcinomatous meningitis, treated
or untreated; Note: brain imaging for asymptomatic patients is not required

- Current symptomatic cord compression requiring surgery or radiation therapy

- Note: once successfully treated and there has been no progression, patients are
eligible for the study

- Active second malignancy (except non-melanomatous skin or superficial bladder cancer)
defined as requiring anticancer therapy or at high risk of recurrence during the study

- Uncontrolled medical conditions such as heart failure, myocardial infarction,
uncontrolled hypertension, disseminated on-going coagulopathy, stroke or treatment of
a major active infection =< 3 months of registration, as well as any significant
concurrent medical illness that in the opinion of the Investigator would preclude
protocol therapy

- Planned concomitant participation in another clinical trial of an experimental agent,
vaccine, or device

- Note: concomitant participation in observational studies is acceptable

- Patients with a global or severe deterioration of health status such that it requires
discontinuation of standard of care treatments for CRPC stage without evidence of
disease progression =< 12 weeks prior to registration