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

NCT02278185 | Completed Phase 2 Results DMC

• 2 other identifiers: 14-0909.ccNCI-2014-02219
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

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.

Conditions

Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Metabolic Syndrome Incidence, Summarized by the Number of Patients With at Least 3 of the 5 Pre-specified Criteria

  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.

  Within the first 12 months of therapy

Secondary Outcomes (12)

• Metabolic Syndrome Incidence, Summarized by the Proportion of Patients With at Least 3 of the 5 Pre-specified Criteria

  Within the first 6 months of therapy

• Change in Bone Turnover Markers, as Measured by Bone-specific Alkaline Phosphatase

  Baseline and month 12

• Change in Bone Density

  Baseline to 12 months

• Change in Free Fat Mass, as Measured by a DXA Scanner

  Baseline to up to 12 months

• Change in Fat Mass, as Measured by a DXA Scanner

  Baseline to up to 12 months

Study Arms (2)

Arm I (enzalutamide)

EXPERIMENTAL

Patients receive enzalutamide PO QD for 12 months in the absence of disease progression or unacceptable toxicity.

Drug: Enzalutamide

Arm II (ADT)

ACTIVE COMPARATOR

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; Drug: goserelin acetate; Drug: histrelin acetate; Drug: triptorelin; Drug: degarelix

Interventions

Enzalutamide DRUG

Given PO

Also known as: MDV3100, selective androgen receptor modulator MDV3100, XTANDI

Arm I (enzalutamide)

leuprolide acetate DRUG

Given SC or IM

Also known as: Enantone, LEUP, Lupron, Lupron Depot

Arm II (ADT)

goserelin acetate DRUG

Given SC or IM

Also known as: ICI-118630, ZDX, Zoladex

Arm II (ADT)

histrelin acetate DRUG

Given SC or IM

Also known as: Supprelin, Vantas

Arm II (ADT)

triptorelin DRUG

Given SC or IM

Also known as: 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, D-TRP-6-LHRH, Decapeptyl, TRIP

Arm II (ADT)

degarelix DRUG

Given SC or IM

Also known as: ASP3550, FE200486, Firmagon

Arm II (ADT)

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (2)

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado Health - Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Leuprolide; Goserelin; histrelin; Triptorelin Pamoate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

This study was originally designed when ADT alone was SOC treatment for metastatic prostate cancer. In the years of opening and enrollment, the SOC changed thus affecting the population of potentially eligible patients.

Results Point of Contact

• Title: Dr. Elizabeth R Kessler
• Organization: University of Colorado School of Medicine

elizabeth.kessler@cuanschutz.edu

720-848-0402

Study Officials

• Elizabeth Kessler, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: October 29, 2014
• Study Start: November 11, 2015
• Primary Completion: April 10, 2019
• Study Completion: July 18, 2024
• Last Updated: May 11, 2025
• Results First Posted: April 27, 2022

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)