Clinical Trials /

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

NCT02059213

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer
  • Official Title: A Randomized Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Hormone-Sensitive Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2013.117
  • SECONDARY ID: HUM00082715
  • NCT ID: NCT02059213

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
IbrancePD 0332991, PalbociclibADT + Ibrance®
BicalutamideCasodexADT Alone
ZoladexGoserelin acetate implantADT Alone
Lupron DepotLeuprolideADT Alone

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
ADT AloneActive ComparatorAndrogen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection).
  • Bicalutamide
  • Zoladex
  • Lupron Depot
ADT + Ibrance®ExperimentalIbrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection).
  • Ibrance
  • Bicalutamide
  • Zoladex
  • Lupron Depot

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 .
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm
Time Frame:28 weeks
Safety Issue:
Description:The primary analysis will be assessment of the proportion of patients who achieve a (Prostate-specific antigen) PSA < 4ng/mL after seven months of protocol treatment in each arm.

Secondary Outcome Measures

Measure:Frequency of Adverse Events
Time Frame:Up to 54 months
Safety Issue:
Description:Frequency of adverse event types will be reported for each arm by attribution and grade.
Measure:Duration of Therapy
Time Frame:Up to 54 months
Safety Issue:
Description:Duration of therapy will be reported to describe tolerability within each arm.
Measure:Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL)
Time Frame:Up to 54 months
Safety Issue:
Description:
Measure:Time to Biochemical Progression
Time Frame:Up to 54 months
Safety Issue:
Description:Biochemical progression-free survival will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first.
Measure:Time to Clinical Progression
Time Frame:Up to 54 months
Safety Issue:
Description:Clinical progression-free survival will begin from treatment start until the event of clinical progression or death, whichever occurs first.
Measure:Frequency of Dose Modification
Time Frame:Up to 54 months
Safety Issue:
Description:Dose modifications will be reported to describe tolerability within each arm.
Measure:Frequency of Treatment Delay
Time Frame:Up to 54 months
Safety Issue:
Description:Treatment delays will be reported to describe tolerability within each arm.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

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