Trial Title:
Study to Determine Possible Effects of Apalutamide, Compared to Placebo, on EGFR Expression in Patients With Non-muscle Invasive Bladder Cancer
NCT ID:
NCT05521698
Condition:
Non-Muscle Invasive Bladder Urothelial Carcinoma
Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Non-Muscle Invasive Bladder Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
The participants and the study team will be blinded.
Intervention:
Intervention type:
Drug
Intervention name:
Apalutamide
Description:
Given PO
Arm group label:
Arm 1 (apalutamide,TURBT)
Other name:
ARN 509
Other name:
ARN-509
Other name:
ARN509
Other name:
Erleada
Other name:
JNJ 56021927
Other name:
JNJ-56021927
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Arm 1 (apalutamide,TURBT)
Arm group label:
Arm 2 (placebo, TURBT)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and urine sample collection
Arm group label:
Arm 1 (apalutamide,TURBT)
Arm group label:
Arm 2 (placebo, TURBT)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Placebo Administration
Description:
Given PO
Arm group label:
Arm 2 (placebo, TURBT)
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm 1 (apalutamide,TURBT)
Arm group label:
Arm 2 (placebo, TURBT)
Intervention type:
Procedure
Intervention name:
Transurethral Resection of Bladder Tumor
Description:
Undergo TURBT
Arm group label:
Arm 1 (apalutamide,TURBT)
Arm group label:
Arm 2 (placebo, TURBT)
Other name:
Transurethral resection (TURBT)
Other name:
TURBT
Summary:
This phase I trial evaluates the effects of apalutamide, compared to placebo, on
epidermal growth factor receptor (EGFR) protein expression 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 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.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare epidermal growth factor receptor (EGFR) messenger ribonucleic acid (mRNA)
expression measured by reverse transcriptase polymerase chain reaction (rt-PCR) in normal
appearing urothelium adjacent to tumor (measured as a ratio relative to urothelium and
lamina-propria specific markers) in participants treated with anti-androgen therapy
versus (vs.) participants given placebo.
SECONDARY OBJECTIVES:
I. To determine effect of apalutamide on EGFR expression (by rtPCR) in the subgroup of
patients whose normal appearing urothelium adjacent to tumor expresses the androgen
receptor (AR) (at least "1" by immunohistochemistry [IHC] score).
II. To correlate AR expression in adjacent urothelium (by IHC score) with EGFR expression
by rtPCR in participants randomized to apalutamide versus placebo.
III. Comparison of toxicity in participants randomized to apalutamide versus placebo.
EXPLORATORY OBJECTIVES:
I. Comparison of AR and EGFR (and possibly phosphorylated EGFR [pEGFR]) staining levels
(low, moderate, high; by immunocytology) in pre-treatment vs. post-treatment bladder wash
cytology.
II. To compare expression of direct androgen response gene (ADAR)-2 measured by rtPCR in
normal appearing adjacent (to tumor) urothelium that does and does not express AR (by
IHC), in participants randomized to apalutamide versus placebo.
III. Ki-67 expression (by IHC) in normal appearing urothelium adjacent to tumor in
participants randomized to apalutamide versus placebo.
IV. Subgroup analysis of Ki-67 expression in the AR+ subgroup. V. Differences in
expression of AR, EGFR, pEGFR, and Ki-67 (by semi-quantitative IHC) in tumor in
participants randomized to apalutamide versus placebo.
VI. Comparison of demographics of two groups. VII. Change in EGFR expression by rt-PCR in
tumor in participants randomized to apalutamide versus placebo.
VIII. Morbidities of treatment (breast tenderness, sexual or urinary side effects,
seizure[s], depression, abnormal liver function tests [LFTs]).
IX. Comparison of pre vs. post intervention urinary biomarkers (CxBladderTM) in both
groups, examining the 5 RNAs (by rtPCR) that make up the test, both as a group and each
RNA separately.
X. Fibroblast growth factor receptor 3 (FGFR3) mutation analysis in deoxyribonucleic acid
(DNA) extracted from formalin fixed paraffin embedded (FFPE) blocks from neighboring
normal urothelium and tumor tissue in participants randomized to apalutamide versus
placebo.
XI. Define changes in the tumor immune microenvironment pre- and post-apalutamide through
liquid biopsies of blood and urine using high-dimensional flow cytometry.
XII. Analyze tumor (biopsy specimen) immune microenvironment via multiplex
immunofluorescence and spatial transcriptomics.
XIII. Compare AR, EGFR, and pEGFR in biopsies of tumors done at index cystoscopy vs.
TURBT in participants randomized to apalutamide versus placebo. (Optional) XIV. Other
exploratory markers such as changes in the urinary microbiome in bladder cancer
participants randomized to apalutamide versus placebo.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive apalutamide orally (PO) once daily (QD) on days 1-21. Patients
undergo TURBT on day 21. Up to 28 days of apalutamide prior to TURBT is permitted in the
absence of unacceptable toxicity. Patients undergo blood and urine sample collection
throughout the study. Patients may optionally undergo tumor biopsy at baseline.
ARM 2: Patients receive placebo PO QD on days 1-21. Patients undergo TURBT on day 21. Up
to 28 days of placebo prior to TURBT is permitted in the absence of unacceptable
toxicity. Patients undergo blood and urine sample collection throughout the study.
Patients may optionally undergo tumor biopsy at baseline.
After completion of study treatment, patients are followed up 20-30 days after TURBT.
Criteria for eligibility:
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 suspected, 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 must wear a
condom when engaging in any activity that allows for passage of ejaculate to another
person throughout the course of the study and 90 days after receiving last dose of
study intervention. Male participants should also be advised of the benefit for a
female partner to use a highly effective method of contraception as a condom may
break or leak. Additionally, men must agree to not donate sperm for the purpose of
reproduction during the study and for a minimum of 90 days after receiving the last
dose of study intervention
- 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
- Any condition (uncontrolled intercurrent illness, psychiatric illness, or social
situation) for which, in the opinion of the investigator, participation would not be
in the best interest of the participant (eg compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments
- History of seizures or central nervous system (CNS) metastasis or any condition that
in the opinion of the investigator may predispose to seizure or treatment with drugs
known to lower the seizure threshold within 4 weeks prior to enrollment in the study
- Participants with severe or unstable angina, myocardial infarction, symptomatic
congestive heart failure, uncontrolled hypertension, long QT, arterial or venous
thromboembolic events (eg pulmonary embolism, cerebrovascular accident including
transient ischemic attacks), or clinically significant ventricular arrhythmias
- In the opinion of the investigator, participant has uncontrolled hypertension, high
cholesterol, or diabetes
- Allergy or hypersensitivity to apalutamide, or excipients, unable or unwilling to
take antiandrogen therapy (ADT)
- Plans to father a child while enrolled in this study or within 12 weeks after the
last dose of study intervention
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Arizona Cancer Center - Prevention Research Clinic
Address:
City:
Tucson
Zip:
85719
Country:
United States
Contact:
Last name:
Juan Chipollini
Phone:
520-694-4032
Email:
jchipollini@surgery.arizona.edu
Investigator:
Last name:
Juan Chipollini
Email:
Principal Investigator
Facility:
Name:
Cedars Sinai Medical Center
Address:
City:
Los Angeles
Zip:
90048
Country:
United States
Contact:
Last name:
Michael A. Ahdoot
Phone:
310-423-2659
Email:
Michael.Ahdoot@cshs.org
Investigator:
Last name:
Michael A. Ahdoot
Email:
Principal Investigator
Facility:
Name:
National Cancer Institute Urologic Oncology Branch
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Contact:
Last name:
Sandeep Gurram
Phone:
240-858-3700
Email:
Sandeep.Gurram@nih.gov
Investigator:
Last name:
Sandeep Gurram
Email:
Principal Investigator
Facility:
Name:
University of Rochester
Address:
City:
Rochester
Zip:
14642
Country:
United States
Contact:
Last name:
Edward M. Messing
Phone:
585-275-3345
Email:
edward_messing@urmc.rochester.edu
Investigator:
Last name:
Edward M. Messing
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Contact:
Last name:
Debasish Sundi
Phone:
219-713-9783
Email:
D.Sundi@osumc.edu
Investigator:
Last name:
Debasish Sundi
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Contact:
Last name:
Kyle A. Richards
Phone:
608-262-0759
Email:
richardsk@urology.wisc.edu
Investigator:
Last name:
Kyle A. Richards
Email:
Principal Investigator
Start date:
April 23, 2025
Completion date:
July 15, 2027
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05521698
