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

This study is not yet open for participant recruitment.
Verified January 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: February 10, 2014
Last verified: January 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: February 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: Eligard, 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: Eligard, Leuprolide

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  • 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 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
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, Michigan
University of Michigan Hospital Not yet 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.         
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: February 10, 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
Leuprolide
Goserelin
Bicalutamide
Nonsteroidal Anti-Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Androgen Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on April 16, 2014