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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05521698
Recruitment Status : Not yet recruiting
First Posted : August 30, 2022
Last Update Posted : January 27, 2023
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
Non-Muscle Invasive Bladder Urothelial Carcinoma Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma Drug: Apalutamide Procedure: Biospecimen Collection Other: Questionnaire Administration Procedure: Transurethral Resection of Bladder Tumor Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Randomized Trial of Apalutamide in Non-Muscle Invasive Bladder Cancer
Estimated Study Start Date : July 24, 2023
Estimated Primary Completion Date : December 1, 2025
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer
Drug Information available for: Apalutamide

Arm Intervention/treatment
Experimental: ARM 1 (apalutamide,TURBT)
Patients receive apalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of treatment is permitted in the absence of unacceptable toxicity. Patients undergo blood specimen collection at baseline and at time of TURBT.
Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • Erleada
  • JNJ 56021927
  • JNJ-56021927

Procedure: Biospecimen Collection
Correlative studies
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Other: Questionnaire Administration
Ancillary studies

Procedure: Transurethral Resection of Bladder Tumor
Undergo TURBT
Other Names:
  • Transurethral resection (TURBT)
  • TURBT

Active Comparator: ARM 2 (TURBT)
Patients undergo TURBT on day 21. Patients undergo blood specimen collection at baseline and at time of TURBT.
Procedure: Biospecimen Collection
Correlative studies
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Other: Questionnaire Administration
Ancillary studies

Procedure: Transurethral Resection of Bladder Tumor
Undergo TURBT
Other Names:
  • Transurethral resection (TURBT)
  • TURBT




Primary Outcome Measures :
  1. The relative Epidermal Growth Factor Receptor (EGFR) expression level [ Time Frame: Up to 28 days ]
    Will be analyzed as a continuous variable. A two-sample Wilcoxon rank-sum test will be conducted to test whether there is significant differences of the log-transformed EGFR expression level 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.) untreated participants.


Secondary Outcome Measures :
  1. Effect of apalutamide on EGFR expression [ Time Frame: Up to 28 days ]
    A two-sample Wilcoxon rank-sum test will be conducted to compare the difference of EGFR expression in androgen receptor (AR) positive participants treated with and without apalutamide

  2. AR expression in adjacent urothelium with EGFR expression in treated and untreated participants. [ Time Frame: Up to 28 days ]
    Pearson correlation and Spearman's rank correlation will be calculated between the AR expression and EGFR expression.

  3. Toxicity of treated to untreated control [ Time Frame: Up to 28 days ]
    Descriptive statistics will be provided for these outcomes.


Other Outcome Measures:
  1. AR and EGFR (and possibly phosphorylated EGFR [pEGFR]) staining levels [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  2. Expression of direct androgen response gene (ADAR)-2 [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  3. Ki-67 expression [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  4. Ki-67 expression in the AR+ subgroup [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  5. Differences in expression of AR, EGFR, pEGFR, and Ki-67 [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  6. Demographics of two groups [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  7. Change in EGFR expression in tumor from treated vs. untreated participants [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  8. Morbidities of treatment [ Time Frame: Up to 28 days ]
    Breast tenderness, sexual or urinary side effects, seizure(s), depression, abnormal liver function tests (LFTs). Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  9. Pre vs. post intervention urinary biomarkers [ Time Frame: Up to 28 days ]
    Comparison of pre vs. post intervention urinary biomarkers (CxBladderTM) in both groups, examining the 5 ribonucleic acids (RNAs) (by rtPCR) that make up the test, both as a group and each RNA separately.

  10. Analysis of fibroblast growth factor receptor 3 (FGFR3) in deoxyribonucleic acid (DNA) [ Time Frame: Up to 28 days ]
    Extracted from fixed paraffin embedded (FFPE) blocks from neighboring normal urothelium and tumor tissue in treated vs. untreated participants. Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  11. Changes in the tumor immune microenvironment pre- and post-apalutamide [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  12. Analysis of tumor (biopsy specimen) infiltrating CD8+ T-cells [ Time Frame: Up to 28 days ]
    Measured by single RNA Sequencing (scRNA-seq) and high dimensional spectral flow cytometry to evaluate TCF1/Tcf7 transcript levels, and perform IHC of CD44+, CD62L, and SLAMF6. Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.

  13. Exploratory markers [ Time Frame: Up to 28 days ]
    Will be summarized by descriptive statistics such as rates and proportions and compared between untreated and apalutamide using nonparametric tests such as the Kurskal-Wallis test.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05521698


Locations
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United States, Arizona
University of Arizona Cancer Center - Prevention Research Clinic
Tucson, Arizona, United States, 85719
Contact: Juan Chipollini    520-694-4032    jchipollini@surgery.arizona.edu   
Principal Investigator: Juan Chipollini         
United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Contact: Michael A. Ahdoot    310-423-2659    Michael.Ahdoot@cshs.org   
Principal Investigator: Michael A. Ahdoot         
United States, Maryland
National Cancer Institute Urologic Oncology Branch
Bethesda, Maryland, United States, 20892
Contact: Sandeep Gurram    240-858-3700    Sandeep.Gurram@nih.gov   
Principal Investigator: Sandeep Gurram         
United States, New York
University of Rochester
Rochester, New York, United States, 14642
Contact: Edward M. Messing    585-275-3345    edward_messing@urmc.rochester.edu   
Principal Investigator: Edward M. Messing         
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Contact: Debasish Sundi    219-713-9783    D.Sundi@osumc.edu   
Principal Investigator: Debasish Sundi         
United States, Wisconsin
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States, 53792
Contact: Kyle A. Richards    608-262-0759    richardsk@urology.wisc.edu   
Principal Investigator: Kyle A. Richards         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Edward M Messing University of Wisconsin, Madison
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05521698    
Other Study ID Numbers: NCI-2022-06871
NCI-2022-06871 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Pending12 ( Other Identifier: University of Wisconsin Carbone Cancer Center )
INT22-09-01 ( Other Identifier: DCP )
P30CA014520 ( U.S. NIH Grant/Contract )
UG1CA242635 ( U.S. NIH Grant/Contract )
First Posted: August 30, 2022    Key Record Dates
Last Update Posted: January 27, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms