Effects of Apalutamide on EGFR Expression in Patients With Non-muscle Invasive Bladder Cancer

• Status: Not yet recruiting
• Trial end date: 2025-04-01
• Target enrollment: 0
• Participant gender: Male

Summary

This phase I trial tests the molecular effects of apalutamide in patients with non-muscle invasive bladder cancer. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Previous studies have suggested that expression of a protein called epidermal growth factor receptor (EGFR) on tumor cells is related to bladder cancer disease progression. This trial may help doctors evaluate if apalutamide has any effect on EGFR expression in patients with non-muscle invasive bladder cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)

Criteria

Inclusion Criteria:

• Biologic male adults ( >= 18 years old)

• Note: Because no dosing or adverse event (AE) data are currently available on the use of apalutamide in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.

• Have suspected non-muscle invasive bladder carcinoma (NMIBC) on clinic-based cystoscopy or imaging as viewed by an American Urological Association (AUA) board-certified urologist

• Have had cross sectional imaging of the abdomen and pelvis (computed tomography [CT] or magnetic resonance imaging [MRI] with or without contrast) within 6 months prior to enrollment with no signs of upper tract urothelial cancer (UC), invasive, nor metastatic disease

• Note: If adenopathy or upper tract abnormalities are identified, a negative biopsy and or ureteroscopy is required prior to enrollment

• Newly diagnosed or occasionally recurrent bladder cancer (BC)

• Note: Occasional recurrence is defined as =< 2 prior NMIBC episodes in the 18 months preceding cystoscopy where the index tumor was identified

• Participants with single and multiple tumor lesions

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1

• Total bilirubin =< 1.5 x institutional upper limit of normal (note: in participants with Gilbert's syndrome, if total bilirubin is > 1.5 x upper limit of normal, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x upper limit of normal, participants may be eligible)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 × institutional upper limit of normal

• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 × institutional upper limit of normal

• Urine Culture < 50,000 colonies/cc of 1 or more organisms (if found and treated and a confirmed negative culture obtained off antibiotics before study drug is started, they will be eligible)

• Serum Testosterone >= 300 ng/dL

• Thyroid stimulating hormone (TSH) within institutional normal

• White blood cell count (WBC) =< 0.5 × institutional lower limit of normal

• The effects of Apalutamide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men who are having sex that can lead to pregnancy must use an acceptable form of contraception (vasectomy with the absence of sperm, sexual abstinence, condoms) throughout the course of the study

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who have had a previous exposure to sex hormone (e.g., exogenous androgens) or anti-androgenic therapies (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, 5 alpha reductase-inhibitors, abiraterone or other anti-androgens) within 6 months of accrual

• Participants who are taking the following medications that increase seizure risks:

(e.g., clozapine, olanzapine, risperidone, ziprasidone),phenothiazine, antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine), bupropion, lithium, meperidine, pethidine, phenothiazine and tricyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline),mirtazapine, selective serotonin reuptake inhibitors (e.g., escitalopram, citalopram, fluoxetine), serotonin norepinephrine reuptake inhibitors (e.g., venlafaxine, desvenlafaxine, levomilnacipran), stimulants (e.g., amphetamines, methylphenidate), monoamine oxidase inhibitors (e.g., phenelzine, selegiline)

• Participants taking any form of anticoagulation (e.g., heparin, warfarin, lovenox, apixaban, rivaroxaban, dabigatran, edoxaban, betrixaban)

• Concurrent use of drugs in category X drug interactions with apalutamide

• Participants receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide

• History of prior or concurrent muscle invading UC, or concurrent prostatic urethral, urethral, or upper tract UC or non-urothelial bladder cancer

• History of radiation therapy to the pelvis, prostate or prostatic bed, or rectum

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements