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Enzalutamide/Leuprolide +/- Abiraterone/Pred in Prostate

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02268175
First received: October 14, 2014
Last updated: November 23, 2016
Last verified: November 2016
  Purpose
This study is comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

Condition Intervention Phase
Prostate Adenocarcinoma
Prostate Cancer
High Risk Prostate Cancer
Drug: Enzalutamide
Drug: Abiraterone Acetate
Drug: Prednisone
Drug: Leuprolide Acetate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Study of Enzalutamide+Leuprolide Versus Enzalutamide+Leuprolide+Abiraterone Acetate+Prednisone as Neoadjuvant Therapy for HIgh-Risk Prostate Cancer Undergoing Prostatectomy

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Percentage of Participants with pCR and MRD [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
    Fisher's exact test


Secondary Outcome Measures:
  • Percentage of participants with pCR at RP [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
  • Percentage of Participants with favorable RCB at RB [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
  • Percentage of Participants with cribriform or intraductal spread at RP [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
  • Percentage of participants with positive surgical margins extracapsular extension, positive seminal vesicles, and positive lymph [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    To evaluate the frequency of positive surgical margins, extracapsular extension, positive seminal vesicles, and positive lymph nodes at time of RP following treatment with ARM 1 compared to ARM 2.

  • Percentage of participants with PSA [ Time Frame: Baseline, Day 169 ] [ Designated as safety issue: No ]
  • Time to biochemical recurrence [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
    Kaplan Meier method and comparison between arms will be conducted by the log-rank test.

  • Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]

Enrollment: 75
Study Start Date: October 2014
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM 1

Participants will be randomized in a 2:1 ratio to neoadjuvant treatment (ARM 1) or (ARM 2).

Participants will receive the assigned study treatment per cycle

  • Enzalutamide- Once daily at prespecified dose, orally
  • Abiraterone Acetate- Once daily at prespecified dose, orally
  • Prednisone-Once daily at prespecified dose, orally
  • Leuprolide Acetate-Intermuscular injection at prespecified dose and duration
Drug: Enzalutamide
160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Can be taken with or without food.
Other Name: XTANDI
Drug: Abiraterone Acetate
1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. No food should be consumed for at least two hours before the dose and for at least one hour after the dose.
Other Name: Zytiga
Drug: Prednisone
5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum.Take with food, preferred to be taken in the morning .
Drug: Leuprolide Acetate
Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Other Names:
  • - Lupron Depot-3 Month
  • - Lupron Depot-4 Month
  • - Lupron Depot
  • - Lupron
  • - Viadur
Experimental: ARM 2

Participants will be randomized in a 2:1 ratio to neoadjuvant treatment (ARM 1) or (ARM 2).

Participants will receive the assigned study treatment per cycle.

  • Enzalutamide- once daily at prespecified dose, orally
  • Leuprolide Acetate- Intermuscular injection at prespecified dose and duration
Drug: Enzalutamide
160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Can be taken with or without food.
Other Name: XTANDI
Drug: Leuprolide Acetate
Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Other Names:
  • - Lupron Depot-3 Month
  • - Lupron Depot-4 Month
  • - Lupron Depot
  • - Lupron
  • - Viadur

Detailed Description:

In this research study, the investigators are comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

Abiraterone acetate with prednisone and enzalutamide are currently FDA-approved for use in the treatment of patients with metastatic castration-resistant prostate cancer, however they are investigational for the treatment of localized prostate cancer. Abiraterone acetate works by decreasing the production of male sex hormones, which cause prostate cancer growth. Enzalutamide works by blocking the effects of male sex hormones, which cause prostate cancer growth.

The FDA (the U.S. Food and Drug Administration) has not approved the combination of enzalutamide and abiraterone acetate as neoadjuvant therapy for high risk prostate cancer undergoing prostatectomy but each drug has been approved for the treatment of more advanced prostate cancer.

Participants will be randomized to one of two study arms. Randomization means that the participant is put into a group by chance. It is like flipping a coin. Neither participant nor the research doctor will choose what group participants are randomized to.

The names of the study medications involved in this study are:

  • Enzalutamide
  • Abiraterone Acetate
  • Prednisone
  • Leuprolide Acetate
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male greater than or equal 18 years of age.
  • Histologically confirmed adenocarcinoma of the prostate without histological variants (including overt neuroendocrine differentiation, small cell neuroendocrine carcinoma features, sarcomatoid features, pure ductal adenocarcinoma, squamous or transitional cell carcinoma).
  • Must have tissue available from the pre-treatment diagnostic biopsy (tissue blocks if possible; if not possible, 10 unstained slides from each positive core sample for a total of 30 slides).
  • Must have three core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within three months from screening.
  • Participants must have the following features:

    • Intermediate-risk disease defined as Gleason 4+3=7 disease OR
    • High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/dL OR T3 disease (by prostate MRI)
  • No evidence of metastatic or nodal disease as determined by radionuclide bone scans CT/MRI.
  • Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
  • ECOG performance status 0 to 1 (Appendix A).
  • Participants must have normal organ and marrow function as defined below:

    • WBC ≥ 3,000/mcL
    • ANC ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL
    • Serum potassium ≥ 3.5 mmol/L
    • AST, ALT, and total bilirubin ≤ 1.5 x Institutional ULN
    • Calculated creatinine clearance ≥ 60 mL/min
    • PTT ≤ 60, INR ≤ 1.5 x Institutional ULN unless on warfarin therapy (investigator would need to determine if safe for participant to stop warfarin prior to biopsy and warfarin therapy)
    • Controlled blood pressure defined as a systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg on no more than three anti-hypertensive agents. Drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulation.

Exclusion Criteria:

  • Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, ARN-509 and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens, LHRH agonist/antagonists. Prior therapy with 5α-reductace inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day 1.
  • Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.
  • Prior systemic treatment with an azole drug within four weeks of screening visit.
  • Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.
  • Clinically significant cardiovascular disease including:
  • Acute coronary syndrome within 6 months of screening visit;

    • Hypotension defined as a systolic blood pressure < 86 mmHg;
    • Bradycardia defined as a heart rate of < 50 beats per minute, unless pharmaceutically induced and thus reversible (i.e. beta blockers);
    • Uncontrolled angina (requiring escalating doses of nitrates) within 3 months of screening visit;
    • Congestive heart failure NYHA Class III or IV or subjects with a history of congestive heart failure NYHA Class III or IV, unless screening ECHO results in left ventricular ejection fraction that ≥ 45%;
    • History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);
    • Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG > 470 msec;
    • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
  • History of seizure or any condition or concurrent medication that may predispose to seizure.
  • Thromboembolism within 6 months of screening visit.
  • Severe hepatic impairment (Child-Pugh Class C).
  • Active or symptomatic viral hepatitis or chronic liver disease.
  • History of pituitary or adrenal dysfunction.
  • GI disorders which may interfere with the absorption of the study drug.
  • Pre-existing condition that warrants long-term corticosteroid use.
  • Concomitant use of medications that may alter pharmacokinetics of abiraterone or enzalutamide.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin.
  • Major surgery or radiation therapy within 30 days of screening.
  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: NCT02268175

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Dana-Farber Cancer Institute
Medivation, Inc.
Investigators
Principal Investigator: Mary-Ellen Taplin, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Mary-Ellen Taplin, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02268175     History of Changes
Other Study ID Numbers: 14-283 
Study First Received: October 14, 2014
Last Updated: November 23, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
prostate adenocarcinoma
advanced prostate cancer
high risk prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Prednisone
Leuprolide
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 07, 2016