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

• ClinicalTrials.gov Identifier: NCT02059213
• Recruitment Status: Completed
• First Posted: February 11, 2014
• Results First Posted: January 28, 2019
• Last Update Posted: September 16, 2020
• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: University of Utah; Vanderbilt-Ingram Cancer Center; Johns Hopkins University; Thomas Jefferson University; Washington University School of Medicine; Northwestern University; City of Hope Comprehensive Cancer Center
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

Tracking Information

• First Submitted Date: February 7, 2014
• First Posted Date: February 11, 2014
• Results First Submitted Date: December 5, 2018
• Results First Posted Date: January 28, 2019
• Last Update Posted Date: September 16, 2020
• Study Start Date: June 2014
• Actual Primary Completion Date: September 9, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2019)

Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm [ Time Frame: 28 weeks ]

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.

Original Primary Outcome Measures (submitted: February 10, 2014)

Number of patients who achieve a PSA < 4ng/mL after seven months of protocol treatment in each arm [ Time Frame: 7 months ]

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. The difference in proportions will be reported with the corresponding 90% exact confidence interval and the Wald asymptotic test of equality.

Current Secondary Outcome Measures (submitted: August 28, 2020)

• Number of Participants With Grade >=3 Adverse Events That Are Possibly, Probably or Definitely Related to Study Treatment [ Time Frame: Up to 54 months ]
  Grade >=3 adverse events that are possibly, probably or definitely related to study treatment, reported by number of participants affected in each arm
• Duration of Therapy [ Time Frame: Up to 54 months ]
  Duration of therapy will be reported to describe tolerability within each arm.
• Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL) [ Time Frame: Up to 54 months ]
• Biochemical Progression-free Survival Rate [ Time Frame: Up to 54 months ]
  12-month biochemical progression-free survival rate will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first. Described by arm using Kaplan-Meier methods.
• Clinical Progression-free Survival Rate [ Time Frame: Up to 54 months ]
  12-month clinical progression-free survival rate will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first. Described by arm using Kaplan-Meier methods.
• Frequency of Dose Modification [ Time Frame: Up to 54 months ]
  Dose modifications will be reported to describe tolerability for arm 2 only (Ibrance®)
• Frequency of Treatment Delay [ Time Frame: Up to 54 months ]
  Treatment delays will be reported to describe tolerability within each arm.

Original Secondary Outcome Measures (submitted: February 10, 2014)

• Frequency of adverse events [ Time Frame: Up to 54 months ]
  Frequency of adverse event types will be reported for each arm by attribution and grade.
• Duration of therapy [ Time Frame: Up to 54 months ]
  Duration of therapy will be reported to describe tolerability within each arm.
• Proportion of patients who achieve undetectable PSA (<0.2ng/mL) [ Time Frame: Up to 54 months ]
• Time to biochemical progression [ Time Frame: Up to 54 months ]
  Biochemical progression-free survival will begin from treatment start until the event of biochemical (PSA) progression or death, whichever occurs first.
• Time to clinical progression [ Time Frame: Up to 54 months ]
  Clinical progression-free survival will begin from treatment start until the event of clinical progression or death, whichever occurs first.
• Frequency of dose modification [ Time Frame: Up to 54 months ]
  Dose modifications will be reported to describe tolerability within each arm.
• Frequency of treatment delay [ Time Frame: Up to 54 months ]
  Treatment delays will be reported to describe tolerability within each arm.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

Brief 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.

• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: Ibrance
  Other Names:

  • PD 0332991
  • Palbociclib
• Drug: Bicalutamide
  Other Name: Casodex
• Drug: Zoladex
  Other Name: Goserelin acetate implant
• Drug: Lupron Depot
  Other Name: Leuprolide

Study Arms

• Active Comparator: ADT Alone
  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).
  Interventions:

  • Drug: Bicalutamide
  • Drug: Zoladex
  • Drug: Lupron Depot
• Experimental: ADT + Ibrance®
  Ibrance® (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).
  Interventions:

  • Drug: Ibrance
  • Drug: Bicalutamide
  • Drug: Zoladex
  • Drug: Lupron Depot

• Publications *: Palmbos PL, Daignault-Newton S, Tomlins SA, Agarwal N, Twardowski P, Morgans AK, Kelly WK, Arora VK, Antonarakis ES, Siddiqui J, Jacobson JA, Davenport MS, Robinson DR, Chinnaiyan AM, Knudsen KE, Hussain M. A Randomized Phase II Study of Androgen Deprivation Therapy with or without Palbociclib in RB-positive Metastatic Hormone-Sensitive Prostate Cancer. Clin Cancer Res. 2021 Jun 1;27(11):3017-3027. doi: 10.1158/1078-0432.CCR-21-0024. Epub 2021 Mar 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 25, 2019): 72
• Original Estimated Enrollment (submitted: February 10, 2014): 60
• Actual Study Completion Date: June 4, 2019
• Actual Primary Completion Date: September 9, 2017 (Final data collection date for primary outcome measure)

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 .

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02059213
• Other Study ID Numbers: UMCC 2013.117; HUM00082715 ( Other Identifier: University of Michigan )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Michigan Rogel Cancer Center
• Original Responsible Party: Maha Hussain, M.D., University of Michigan Rogel Cancer Center, Cis Maisel Professor of Oncology, Professor of Internal Medicine and Professor of Urology, Medical School
• Current Study Sponsor: University of Michigan Rogel Cancer Center
• Original Study Sponsor: Same as current

Collaborators

• University of Utah
• Vanderbilt-Ingram Cancer Center
• Johns Hopkins University
• Thomas Jefferson University
• Washington University School of Medicine
• Northwestern University
• City of Hope Comprehensive Cancer Center

Investigators

• Principal Investigator: Maha Hussain, MD, FACP, FASCO; University of Michigan Comprehensive Cancer Center and Northwestern University

• PRS Account: University of Michigan Rogel Cancer Center
• Verification Date: August 2020