Enzalutamide Before Surgery in Treating Patients With Kidney Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
PRIMARY OBJECTIVES:
- 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 Design
Arms and Interventions
| 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. |
Drug: Enzalutamide
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Procedure: Nephrectomy
Undergo partial or radical nephrectomy
|
Outcome Measures
Primary Outcome Measures
- Cell proliferation [Up to 36 months]
- Tumor apoptosis as measured by annexin [Up to 36 months]
Secondary Outcome Measures
- Incidence of adverse events (AEs) as assessed by Common Terminology Criteria for Adverse Events version 4 [Up to 36 months]
Post-operative complications will be documented according to the Clavien-Dindo Classification System.
- Tumor size as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [Up to 36 months]
Other Outcome Measures
- AR expression measured in pre- and post-treatment tissue samples by immunohistochemistry (IHC) [Up to 36 months]
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.
- 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 [Up to 36 months]
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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
Sponsors and Collaborators
- Rutgers, The State University of New Jersey
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Eric Singer, Rutgers Cancer Institute of New Jersey
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro20170000806
- NCI-2016-01113
- 081604
- P30CA072720