A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer

Patients will undergo exams, tests, and procedures to determine if they are eligible to
participate. Subjects will be randomized to one of two groups. Patients randomized to Arm 1 -
Patients will receive the LHRH agonist every 3 months. Patients will also take 50 mg. of
bicalutamide by mouth every day. Bicalutamide comes in tablet form. This arm is broken down
into periods of time called cycles, starting with cycle 1 then cycle 2, and so on.Each cycle
is 28 days long. If randomized to Arm 2 - Patients will receive the LHRH agonist every 3
months. Patients will also take 50 mg. of bicalutamide by mouth every day. Patients will also
take 125 mg. of Ibrance® daily for 21 days, and then will stop taking Ibrance® for 7 days.
Patients will then begin taking Ibrance® again after 7 days off. Patients will keep repeating
this cycle every 28 days. When the patient starts the first 28 day cycle that will be cycle
1, then cycle 2, and so on. During each cycle the patient will come in for routine and
research tests and procedures for patient safety, to see how patients are doing, and for
research purposes. The researchers will ask patients to complete a drug diary to track
bicalutamide and Ibrance® administration. The total time of study participation depends on
how a patient responds to the study medications. Patients may be on the study for a short
period of time, such as a week, or for a longer period of time, such as a few years. Patients
may continue on study treatment until one of the following: cancer progresses (gets worse);
another illness or condition develops that prevents study participation; unacceptable side
effects occur; drug is delayed more than 4 weeks; patient withdraws consent; the study doctor
thinks the patient should stop; the patient does not follow researcher's instructions; the
study is cancelled.

Inclusion Criteria:

- Have pathologic diagnosis of prostate cancer.

- Have hormone-sensitive metastatic disease (M1) as evidenced by soft tissue and/or bony
metastases.

- Patients may either be untreated for their newly diagnosed metastatic disease
(preferred as much as possible) or have started androgen deprivation therapy. Patients
who have started androgen deprivation therapy for the treatment of their newly
diagnosed metastatic disease are eligible as long as the duration of treatment is less
than or equal to 2 weeks (14days) prior to registration. The start date of androgen
deprivation is considered the day the patient first received an injection of a LHRH
agonist/antagonist (or orchiectomy), not the date when an oral antiandrogen started.

- Patients must have a minimum PSA (Prostate-Specific Antigen) ≥ 5 ng/mL within 60 days
of registration or prior to the initiation of androgen deprivation for patients who
have started androgen deprivation therapy.

- Agree to undergo a biopsy of at least one metastatic site for RB (Retinoblastoma
Protein) status evaluation. Adequate metastatic tissue from prior biopsy/resection can
be used if available in lieu of a biopsy.

- ECOG performance status of 0-2 (Eastern Cooperative Oncology Group scoring system used
to quantify general well-being and activities of daily life; scores range from 0 to 5
where 0 represents perfect health and 5 represents death).

- Patients may have received prior neoadjuvant and/or adjuvant hormonal therapy, for
non-metastatic disease but it must not have lasted for more than 36 months. At least
12 months must have elapsed since completion of androgen deprivation therapy in the
neoadjuvant and/or adjuvant setting.

- Within 14 days prior to registration patients must have adequate organ and marrow
function: White Blood Cell (WBC) count ≥ 3,000/μl, Absolute Neutrophil Count (ANC) ≥
1,500/μl, Platelet Count ≥ 100,000/μl, Serum Creatinine ≥1.5 x the institutional upper
limits of normal or corrected creatinine clearance of ≥ 50 mg/ml/hr/1.73 m2 BSA (Body
Surface Area), Bilirubin within the institutional limits of normal, AST (Aspartate
Aminotransferase) ≤ 2 x upper limits of normal, ALT (Alanine Aminotransferase) ≤ 2 x
upper limits of normal.

- Patients must be able to take oral medication without crushing, dissolving or chewing
tablets.

- Patients may have received prior radiation therapy or surgery. However, at least 14
days must have elapsed since completion of radiation therapy or surgery and patient
must have only grade 2 or less adverse effects at the time of registration.

- Patients must agree to use highly effective contraception during treatment and for a
period of 90 days after ending treatment with PD 0332991.

- Ability to understand and the willingness to sign a written informed consent document
that is approved by an institutional review board.

Exclusion Criteria:

- Patients who have received androgen deprivation therapy for greater than 14 days
(LHRH-agonist or antagonist) for the treatment of their newly diagnosed metastatic
disease prior to enrollment are not eligible for this study.

- Patients who are currently being treated with strong CYP3A4 inhibitors (e.g.,
amprenavir, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir,
mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir,
telaprevir, telithromycin, verapamil, voriconazole, and grapefruit) or strong inducers
(e.g., carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone,
rifabutin, rifampin, rifapentine and St. John's wort) must either discontinue these
drugs or are ineligible.

- Patients must refrain from the use of proton pump inhibitors. If needed, alternative
antacid therapies may be used including H2-receptor antagonists, and locally acting
antacids.

- 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.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure (New York Heart Association Class III
and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

- Patients with a "currently active" second malignancy other than non-melanoma skin
cancers are not eligible. Patients are not considered to have a "currently active"
malignancy if they have completed all therapy and are now considered without evidence
of disease for 1 year.

- HIV-positive patients on combination antiretroviral therapy are ineligible .