Enzalutamide/Leuprolide +/- Abiraterone/Pred in Prostate

NCT02268175 | Completed Phase 2 Results DMC

• 1 other identifier: 14-283
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 4

Brief Summary

This study is comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

Conditions

Prostate Adenocarcinoma; Prostate Cancer; High Risk Prostate Cancer

Keywords

prostate adenocarcinoma; advanced prostate cancer; high risk prostate cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Pathologic Complete Response (pCR) or Minimal Residual Disease (MRD)

  pCR is defined as the absence of morphologically identifiable carcinoma in the radical prostatectomy (RP) specimen. MRD is defined as the largest cross-sectional dimension of residual tumor measuring \</= 0.5 cm. If the tumor is multifocal, the size of the largest focus will be used to determine the size of the residual tumor.

  after RP approximately 24 weeks from study entry

Secondary Outcomes (4)

• Participants With Pathologic Complete Response (pCR)

  after RP approximately 24 weeks from study entry

• Residual Cancer Burden (RCB)

  after RP approximately 24 weeks from study entry

• Positive Surgical Margin Status

  after RP approximately 24 weeks from study entry

• Median Prostate Specific Antigen (PSA) Nadir

  PSA was assessed at baseline and every cycle during neoadjuvant therapy (up to 24 weeks).

Study Arms (2)

ARM 1

EXPERIMENTAL

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; Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Leuprolide Acetate

ARM 2

EXPERIMENTAL

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; Drug: Leuprolide Acetate

Interventions

Enzalutamide DRUG

160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Can be taken with or without food.

Also known as: XTANDI

ARM 1; ARM 2

Abiraterone Acetate DRUG

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.

Also known as: Zytiga

ARM 1

Prednisone DRUG

5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum.Take with food, preferred to be taken in the morning .

ARM 1

Leuprolide Acetate DRUG

Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.

Also known as: - Lupron Depot-3 Month, - Lupron Depot-4 Month, - Lupron Depot, - Lupron, - Viadur

ARM 1; ARM 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Medivation, Inc.: collaborator

Study Sites (4)

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• McKay RR, Ye H, Xie W, Lis R, Calagua C, Zhang Z, Trinh QD, Chang SL, Harshman LC, Ross AE, Pienta KJ, Lin DW, Ellis WJ, Montgomery B, Chang P, Wagner AA, Bubley GJ, Kibel AS, Taplin ME. Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone. J Clin Oncol. 2019 Apr 10;37(11):923-931. doi: 10.1200/JCO.18.01777. Epub 2019 Feb 27.

  PMID: 30811282 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Abiraterone Acetate; Prednisone; Leuprolide

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)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; 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

Results Point of Contact

• Title: Mary-Ellen Taplin, MD
• Organization: Dana-Farber Cancer Institute

mary_taplin@dfci.harvard.edu

617-582-7221

Study Officials

• Mary-Ellen Taplin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 20, 2014
• Study Start: October 1, 2014
• Primary Completion: January 1, 2018
• Study Completion: December 1, 2021
• Last Updated: April 19, 2022
• Results First Posted: October 8, 2019

Record last verified: 2022-03

Locations

US (4)