A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Ibrance; Bicalutamide; Zoladex; Lupron Depot
Intervention MeSH terms: Palbociclib; Leuprolide; Goserelin; Bicalutamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will look at the effect of adding the drug Palbociclib to CAD (Combined Androgen
      Deprivation) therapy in patients with RB (Retinoblastoma Protein) positive hormone sensitive
      prostate cancer.

      The investigators hypothesize that the addition of Palbociclib to initial ADT (Androgen
      Deprivation Therapy) in patients with newly metastatic RB-positive prostate cancer may
      significantly increase the efficacy of ADT.
    

Eligibility criteria:

        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 .