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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Ibrance; Drug: Bicalutamide; Drug: Zoladex; Drug: Lupron Depot	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Hormone-Sensitive Prostate Cancer
• Study Start Date: June 2014
• Actual Primary Completion Date: September 9, 2017
• Actual Study Completion Date: June 4, 2019

Arms and Interventions

Arm	Intervention/treatment
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).	Drug: Bicalutamide; Other Name: Casodex; Drug: Zoladex; Other Name: Goserelin acetate implant; Drug: Lupron Depot; Other Name: Leuprolide
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).	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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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
2. Duration of Therapy [ Time Frame: Up to 54 months ]
   Duration of therapy will be reported to describe tolerability within each arm.
3. Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL) [ Time Frame: Up to 54 months ]
4. 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.
5. 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.
6. Frequency of Dose Modification [ Time Frame: Up to 54 months ]
   Dose modifications will be reported to describe tolerability for arm 2 only (Ibrance®)
7. Frequency of Treatment Delay [ Time Frame: Up to 54 months ]
   Treatment delays will be reported to describe tolerability within each arm.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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 .

Contacts and Locations

Locations

United States, California

City of Hope Cancer Center

Duarte, California, United States, 91010

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Maryland

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

United States, Michigan

University of Michigan Hospital

Ann Arbor, Michigan, United States, 48109

United States, Missouri

Washington University in St. Louis

Saint Louis, Missouri, United States, 63110

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Utah

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

University of Michigan Rogel Cancer Center

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

  Study Documents (Full-Text)

Documents provided by University of Michigan Rogel Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] August 9, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT02059213
• Other Study ID Numbers: UMCC 2013.117; HUM00082715 ( Other Identifier: University of Michigan )
• First Posted: February 11, 2014
• Results First Posted: January 28, 2019
• Last Update Posted: September 16, 2020
• Last Verified: August 2020

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Palbociclib; Leuprolide; Goserelin; Bicalutamide; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Androgen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists