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Enzalutamide Versus Standard Androgen Deprivation Therapy for the Treatment Hormone Sensitive Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02278185
Recruitment Status : Active, not recruiting
First Posted : October 29, 2014
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
This randomized phase II trial compares enzalutamide with standard androgen deprivation therapy in reducing incidence of metabolic syndrome in patients with prostate cancer that has spread to other places in the body. Metabolic syndrome is defined as changes in cholesterol, blood pressure, circulating sugar levels, and body weight. Previous studies have shown that patients with prostate cancer, who have been treated with standard medical therapy that lowers testosterone levels, have an increased risk of these changes. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells instead of lowering testosterone levels. It is not yet known whether prostate cancer patients who receive enzalutamide will have reduced incidence of metabolic syndrome than patients who receive standard androgen deprivation therapy.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Prostate Recurrent Prostate Cancer Stage III Prostate Cancer Stage IV Prostate Cancer Drug: Enzalutamide Drug: leuprolide acetate Drug: goserelin acetate Drug: histrelin acetate Drug: triptorelin Drug: degarelix Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the incidence of metabolic syndrome within 12 months, as defined by the Adult Treatment Panel III, in patients treated with enzalutamide compared to standard androgen deprivation therapy.

SECONDARY OBJECTIVES:

I. To determine the incidence of metabolic syndrome within 6 months, as defined by the Adult Treatment Panel III, in patients treated with enzalutamide compared to standard androgen deprivation therapy.

II. To assess bone health, as measured by a dual-energy x-ray absorptiometry (DXA) scanner.

III. To assess body composition (sarcopenic obesity), as measured by a DXA scanner.

IV. To assess quality of life (QOL), as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Sexual Health Inventory in Men (SHIM).

V. To assess time to prostate-specific antigen (PSA) progression and time to radiographic progression.

VI. To assess the incidence of developing individual risk factors, or components, which comprise metabolic syndrome.

VII. To assess the change in high-sensitivity C-reactive protein (hs-CRP) as a marker of inflammation.

VIII. To assess the safety and tolerance of enzalutamide or androgen deprivation therapy (ADT).

IX. To assess the change in physical function as measured by the Short Physical Performance Battery (SPPB).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive enzalutamide orally (PO) once daily (QD) for 12 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.

After completion of study treatment, patients are followed up at 30 days.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: An Open Label, Randomized, Phase II Trial of Metabolic Complications in Patients Treated With Enzalutamide vs Standard ADT for the Treatment of Hormone Sensitive Prostate Cancer
Actual Study Start Date : November 11, 2015
Actual Primary Completion Date : February 25, 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (enzalutamide)
Patients receive enzalutamide PO QD for 12 months in the absence of disease progression or unacceptable toxicity.
Drug: Enzalutamide
Given PO
Other Names:
  • MDV3100
  • selective androgen receptor modulator MDV3100
  • XTANDI

Active Comparator: Arm II (ADT)
Patients receive standard of care ADT comprising one of the following at the discretion of the treating physician: leuprolide acetate, goserelin acetate, histrelin acetate, triptorelin, or degarelix SC or IM for 12 months in the absence of disease progression or unacceptable toxicity. Patients may also choose to undergo surgical castration as an alternative form of ADT.
Drug: leuprolide acetate
Given SC or IM
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot

Drug: goserelin acetate
Given SC or IM
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex

Drug: histrelin acetate
Given SC or IM
Other Names:
  • Supprelin
  • Vantas

Drug: triptorelin
Given SC or IM
Other Names:
  • 6-D-Tryptophan-LH-RH
  • 6-D-Tryptophanluteinizing Hormone-releasing Factor
  • D-TRP-6-LHRH
  • Decapeptyl
  • TRIP

Drug: degarelix
Given SC or IM
Other Names:
  • ASP3550
  • FE200486
  • Firmagon




Primary Outcome Measures :
  1. Metabolic syndrome incidence, summarized by the proportion of patients with at least 3 of the 5 pre-specified criteria [ Time Frame: Within the first 12 months of therapy ]
    Metabolic syndrome will be assessed at the beginning of each course and defined by the presence of 3 of the following five traits: abdominal obesity, defined as a waist circumference > 102 cm (> 40 in); serum triglycerides >= 150 mg/dL (1.7 mmol/L) or drug treatment for elevated triglycerides; serum high density lipoprotein (HDL) cholesterol < 40 mg/dL (1 mmol/L) or drug treatment for low HDL; blood pressure >= 130/>= 85 mmHg or drug treatment for elevated blood pressure; and fasting plasma glucose (FPG) >= 100 mg/dL (5.6 mmol/L) or drug treatment for elevated blood glucose.


Secondary Outcome Measures :
  1. Metabolic syndrome incidence, summarized by the proportion of patients with at least 3 of the 5 pre-specified criteria [ Time Frame: Within the first 6 months of therapy ]
    Metabolic syndrome will be assessed at the beginning of each course and defined by the presence of 3 of the following five traits: abdominal obesity, defined as a waist circumference > 102 cm (> 40 in); serum triglycerides >= 150 mg/dL (1.7 mmol/L) or drug treatment for elevated triglycerides; serum HDL cholesterol < 40 mg/dL (1 mmol/L) or drug treatment for low HDL; blood pressure >= 130/>= 85 mmHg or drug treatment for elevated blood pressure; and FPG >= 100 mg/dL (5.6 mmol/L) or drug treatment for elevated blood glucose.

  2. Change in bone turnover markers, as measured by bone-specific alkaline phosphatase and N-telopeptide [ Time Frame: Baseline to up to 12 months ]
    Will be assessed for each treatment group. Measurements will be taken at day 1 of each course and reported as a continuous variable. A paired t-test will test within an arm as to whether the change from baseline to each time point is significantly different from zero.

  3. Change in bone density, as measured by a DXA scanner [ Time Frame: Baseline to up to 12 months ]
    A paired t-test will test within an arm as to whether the change from baseline to each time point is significantly different from zero.

  4. Change in free fat mass, as measured by a DXA scanner [ Time Frame: Baseline to up to 12 months ]
    A paired t-test will test within an arm as to whether the change from baseline to each time point is significantly different from zero.

  5. Change in fat mass, as measured by a DXA scanner [ Time Frame: Baseline to up to 12 months ]
    A paired t-test will test within an arm as to whether the change from baseline to each time point is significantly different from zero.

  6. Change in QOL scores, as measured by the FACT-P and SHIM [ Time Frame: Baseline to up to 12 months ]
    Will be assessed in each treatment group.

  7. Median time to PSA progression [ Time Frame: Time from randomization to the earliest objective evidence of PSA progression as defined per protocol, assessed up to 30 days after the last dose of study drug ]
    PSA progression as defined by an increase in >= 50% from nadir and an absolute increase of at least 2 ng/mL above the nadir, occurring at least 12 weeks after start of therapy that is confirmed by two consecutive increases taken at least 2 weeks apart. Log rank test will be used to compare the distributions of above variables between the group treated with enzalutamide to the group on standard ADT.

  8. Time to radiographic progression [ Time Frame: Time from randomization to the earliest objective evidence of radiographic progression as defined per protocol, assessed up to 30 days after the last dose of study drug ]
    Log rank test will be used to compare the distributions of above variables between the group treated with enzalutamide to the group on standard ADT.

  9. Change in markers of inflammation, as measured by circulating hs-CRP [ Time Frame: Baseline to up to 12 months ]
  10. Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.1 [ Time Frame: Up to 30 days after the last dose of study drug ]
    Adverse events data will be summarized using tables and descriptive statistics. Individual toxicities will be summarized by their frequency and intensity for each treatment group.

  11. Change in physical function, as measured by SPPB [ Time Frame: Baseline to up to 12 months ]
    The SPPB incorporates 3 validated portions to assess a patient's balance and mobility. Will be measured as a continuous outcome.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically proven adenocarcinoma of the prostate; if pathology is unavailable, the principal investigator (PI) may also make a determination of prostate cancer based on unequivocal clinic data
  • Patients with advanced prostate cancer suitable for systemic treatment defined as: having metastatic disease, a biochemical relapse after primary therapy, or patients in whom primary therapy is not appropriate or feasible; patients without metastatic disease will need evaluation for local therapy and deemed inappropriate or have refused this treatment option
  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Age > 18 years
  • Must use a condom if having sex with a pregnant woman
  • A male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration
  • Life expectancy estimated at > 12 months
  • Ability to understand and willingness to provide written informed consent document

Exclusion Criteria:

  • A history of androgen deprivation therapy; patients receiving hormonal therapy in the adjuvant and/or neoadjuvant setting must have discontinued therapy at least 6 months prior to day 1 of treatment AND have a serum testosterone level >= 50 ng/dL AND cannot have received more than 18 months of previous ADT
  • A history of orchiectomy
  • Previous androgen blockade (e.g. antiandrogens) in the last 3 months
  • Patients already meeting the criteria for metabolic syndrome as defined by the Adult Treatment Panel III Criteria which requires 3/5 parameters encompassing glucose control, blood pressure, lipids and waist circumference; patients with 2 of the parameters at baseline will be allowed enrollment provided that one of those risk factors is hypertension (>= 130/>= 85 mm Hg)
  • Baseline hypogonadism as defined as a testosterone < 50 ng/dL
  • PSA < 0.5 ng/dL
  • Serum vitamin D 25, hydroxy (OH) < 12 ng/mL
  • Active hepatitis C virus
  • Use of corticosteroids as defined by a daily dose of prednisone (or equivalent) of 5 mg or greater for more than 1 month continuously within 3 months of screening
  • Corrected calcium > 10.6 mg/dL
  • Absolute neutrophil count < 1500/uL
  • Platelet count < 100,000/uL
  • Hemoglobin < 9 g/dL
  • Total bilirubin >= 1.5 x upper limit of normal (ULN) (unless documented Gilbert's)
  • Alanine aminotransferase or aspartate aminotransferase >= 2.5 x ULN
  • Creatinine > 2 mg/dL
  • Clinically significant cardiovascular disease as evidenced by: myocardial infarction within 6 months of screening; uncontrolled angina within 3 months of screening; New York Heart Association (NYHA) class 3 or 4 congestive heart failure; clinically significant ventricular arrhythmia; Mobitz II/2nd degree/or 3rd degree heart block without a pacemaker in place; uncontrolled hypertension (HTN) (systolic > 180 mmHg or diastolic > 105 mmHg at screening)
  • Previous exposure to enzalutamide
  • Use of an investigational therapeutic within 30 days
  • History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agent
  • Known or suspected brain metastasis or active leptomeningeal disease
  • History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past; also, history of loss of consciousness or transient ischemic attack within 12 months of day 1 visit
  • Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02278185


Locations
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United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
University of Colorado Health - Poudre Valley Hospital
Fort Collins, Colorado, United States, 80524
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Elizabeth Kessler, MD University of Colorado, Denver

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02278185    
Other Study ID Numbers: 14-0909.cc
NCI-2014-02219 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: October 29, 2014    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Leuprolide
Goserelin
Triptorelin Pamoate
Hormones
Androgens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents