A Phase II Study of Androgen Deprivation Therapy With or Without PD 0332991 in RB-Positive Metastatic Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Michigan Cancer Center
Sponsor:
Collaborators:
University of Utah
Vanderbilt-Ingram Cancer Center
Dana-Farber Cancer Institute
Johns Hopkins University
Thomas Jefferson University
Information provided by (Responsible Party):
Maha Hussain, M.D., University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT02059213
First received: February 7, 2014
Last updated: July 16, 2014
Last verified: June 2014
  Purpose

This study will look at the effect of adding the drug PD 0332991 to CAD (Combined Androgen Deprivation) therapy in patients with RB (Retinoblastoma Protein) positive hormone sensitive prostate cancer.

The investigators hypothesize that the addition of PD 0332991 to initial ADT (Androgen Deprivation Therapy) in patients with newly metastatic RB-positive prostate cancer may significantly increase the efficacy of ADT.


Condition Intervention Phase
Prostate Cancer
Drug: PD 0332991
Drug: Bicalutamide
Drug: Zoladex
Drug: Lupron Depot
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Androgen Deprivation Therapy With or Without PD 0332991 in RB-Positive Metastatic Hormone-Sensitive Prostate Cancer

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Number of patients who achieve a PSA < 4ng/mL after seven months of protocol treatment in each arm [ Time Frame: 7 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Frequency of adverse events [ Time Frame: Up to 54 months ] [ Designated as safety issue: Yes ]
    Frequency of adverse event types will be reported for each arm by attribution and grade.

  • Duration of therapy [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Time to biochemical progression [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Dose modifications will be reported to describe tolerability within each arm.

  • Frequency of treatment delay [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]
    Treatment delays will be reported to describe tolerability within each arm.


Estimated Enrollment: 60
Study Start Date: June 2014
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 + PD 0332991
PD 0332991 (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: PD 0332991
Other Name: Pablociclib
Drug: Bicalutamide
Other Name: Casodex
Drug: Zoladex
Other Name: Goserelin acetate implant
Drug: Lupron Depot
Other Name: Leuprolide

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 PD0332991 daily for 21 days, and then will stop taking PD0332991 for 7 days. Patients will then begin taking PD0332991 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 PD0332991 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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 prior to initiation of androgen deprivation therapy.
  • Patients must have a minimum PSA (Prostate-Specific Antigen) ≥ 5 ng/mL obtained within 60 days prior to study registration.
  • 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, and serum testosterone must be within the institutional normal range.
  • 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 within the past 12 months 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02059213

Contacts
Contact: Maha Hussain, M.B., Ch.B. 734-936-8906 mahahuss@umich.edu

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Not yet recruiting
Baltimore, Maryland, United States, 21231
Contact: Emmanuel Antonarakis, MD    410-502-7528    eantona1@jhmi.edu   
Principal Investigator: Emmanuel Antonarakis, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Mary-Ellen Taplin, MD    617-632-3237    Mary_taplin@dfci.harvard.edu   
Principal Investigator: Mary-Ellen Taplin, MD         
United States, Michigan
University of Michigan Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Maha Hussain, M.B., Ch.B.    734-936-8906    mahahuss@umich.edu   
Principal Investigator: Maha Hussain, M.B., Ch.B.         
United States, Pennsylvania
Thomas Jefferson University Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Wm. Kevin Kelly, DO    215-503-5455    wm.kevin.kelly@jefferson.edu   
Principal Investigator: Wm. Kevin Kelly, DO         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Alicia K. Morgans, MD    615-322-4967    alicia.morgans@vanderbilt.edu   
Principal Investigator: Alicia K. Morgans, MD         
United States, Utah
Huntsman Cancer Institute, University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84112
Contact: Neeraj Agarwal, MD    801-585-9682    Neeraj.Agarwal@hci.utah.edu   
Principal Investigator: Neeraj Agarwal, MD         
Sponsors and Collaborators
University of Michigan Cancer Center
University of Utah
Vanderbilt-Ingram Cancer Center
Dana-Farber Cancer Institute
Johns Hopkins University
Thomas Jefferson University
Investigators
Principal Investigator: Maha Hussain, M.B., Ch.B. University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Maha Hussain, M.D., Cis Maisel Professor of Oncology, Professor of Internal Medicine and Professor of Urology, Medical School, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT02059213     History of Changes
Other Study ID Numbers: UMCC 2013.117, HUM00082715
Study First Received: February 7, 2014
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Bicalutamide
Goserelin
Leuprolide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Androgen Antagonists
Hormone Antagonists
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on September 16, 2014