Enzalutamide Before Surgery in Treating Patients With Kidney Cancer

Pilot Study of the Blockade of Androgens in Renal Cell Carcinoma Using Enzalutamide (BARE)

This pilot phase 0 trial studies how well enzalutamide works before surgery in treating patients with kidney cancer. Androgens are a type of hormone produced by the body that may cause kidney tumors to grow. Anti-hormone therapy, such as enzalutamide, may lessen the amount of androgens produced by the body and keep kidney tumors from growing.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Renal Cell Carcinoma; Stage I Renal Cell Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Enzalutamide; Procedure: Nephrectomy

Detailed Description

PRIMARY OBJECTIVES:

I. To investigate the effects of neoadjuvant enzalutamide on clear cell renal cell carcinoma (ccRCC).

OUTLINE:

Patients receive enzalutamide orally (PO) daily for 90 days in the absence of disease progression or unacceptable toxicity. Patients then undergo partial or radical nephrectomy.

After completion of study treatment, patients are followed up every 3 months.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical T1N0M0 (=< 7 cm) renal mass as measured on cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI])
• Biopsy proven ccRCC
• Tumor with androgen receptor (AR) expressed >= 4580 copies/ug ribonucleic acid (RNA)
• Can provide informed consent
• Adequate hepatic function (>= 1.5 x upper limit of normal [ULN]; patient's with Gilbert's disease are not excluded)
• Adequate renal function (estimated glomerular filtration rate [GFR] > 40mL/min)
• No evidence of metastatic disease on baseline imaging (chest x-ray [CXR] or chest CT, abdominal CT or MRI)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Exclusion Criteria:

• Prior use of androgen deprivation including enzalutamide
• Pregnant women or women who are of child bearing age who are not willing to use two (2) forms of contraception during treatment with enzalutamide and for six (6) months after treatment
• Men must use adequate methods of contraception during and at least 3 months after treatment if engaging in sexual activity with a female of child bearing age
• Known hypersensitivity to enzalutamide
• History of unprovoked deep vein thrombosis/pulmonary embolism (DVT/PE) in past twelve (12) months
• Inability to stop anticoagulants/antiplatelet therapy peri-operatively
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma)
• History of loss of consciousness or transient ischemic attack within twelve (12) months of enrollment
• Any unstable, serious co-existing medical conditions including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within twelve (12) months prior to screening
• Known or suspected brain metastasis or active leptomeningeal disease
• Current use of exogenous testosterone
• Retroperitoneal/hilar adenopathy concerning for locally advanced disease
• Metastatic RCC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (enzalutamide, nephrectomy); Patients receive enzalutamide PO daily for 90 days in the absence of disease progression or unacceptable toxicity. Patients then undergo partial or radical nephrectomy.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Enzalutamide; Given PO; Other Names: Xtandi; MDV3100; ASP9785; Procedure: Nephrectomy; Undergo partial or radical nephrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cell proliferation	Up to 36 months
Tumor apoptosis as measured by annexin	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) as assessed by Common Terminology Criteria for Adverse Events version 4	Post-operative complications will be documented according to the Clavien-Dindo Classification System.	Up to 36 months
Tumor size as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		Up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AR expression measured in pre- and post-treatment tissue samples by immunohistochemistry (IHC)	Pre- and post-treatment ccRCC samples will be used to purify mRNA, construct cDNA, and perform qPCR to quantify expression of mRNA. IHC staining will be performed on ccRCC pre- and post-treatment.	Up to 36 months
Genome-wide analysis of post-treatment tissue samples assessed by whole exome and RNA sequencing		Up to 36 months
Intracrine androgen signaling levels of testosterone and dihydrotestosterone assessed in tissue	Pre- and post-treatment tissue levels of testosterone and dihydrotestosterone will be compared to their respective serum levels to assess intracrine androgen signaling in ccRCC following enzalutamide treatment.	Up to 36 months

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Eric Singer, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2017
• Primary Completion (Actual): March 2, 2020
• Study Completion (Actual): March 2, 2020

Study Registration Dates

• First Submitted: August 26, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): August 31, 2016

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: Pro20170000806; P30CA072720 (U.S. NIH Grant/Contract); NCI-2016-01113 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 081604 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No