Apalutamide for Bladder Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antipsychotics, Antidepressants, Anticoagulants, others

Disqualifiers: Seizures, Muscle invading UC, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: 4 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications that increase seizure risks, anticoagulants, and any drugs that have severe interactions with apalutamide. If you are on these medications, you may need to stop them before participating.

What data supports the effectiveness of the drug Apalutamide for bladder cancer?

Apalutamide is known to be effective in treating prostate cancer by blocking androgen receptors, which are also involved in bladder cancer progression. Another drug, enzalutamide, which works similarly to apalutamide, has shown promise in slowing the growth of bladder cancer cells, suggesting that apalutamide might have similar effects. ^{1 2 3 4 5}

How is the drug Apalutamide unique for treating bladder cancer?

Apalutamide is unique because it is an oral drug that targets androgen receptors, which are proteins that can promote cancer growth, and it has been primarily used for prostate cancer. Its use in bladder cancer is novel, as there is limited information on androgen receptor inhibitors like Apalutamide being used for this condition. ^{1 2 3 4 5}

Research Team

Edward M Messing

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for biologic male adults with non-muscle invasive bladder cancer, who are in good health and have not had certain treatments or conditions that could interfere with the study. They must be able to sign consent, have no signs of advanced disease on recent scans, and agree to use contraception.

Inclusion Criteria

Your testosterone levels are at least 300 ng/dL.

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

I have one or more tumors.

Exclusion Criteria

I have had radiation therapy to my pelvis, prostate, or rectum.

I haven't taken hormone therapies or anti-hormone treatments in the last 6 months.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide or placebo orally once daily for up to 28 days, with TURBT on day 21

4 weeks

Daily oral administration, TURBT on day 21

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1-2 visits (in-person or virtual)

Treatment Details

Interventions

• Apalutamide

Trial Overview The trial is testing if Apalutamide affects a protein called EGFR in patients with non-muscle invasive bladder cancer. It includes biospecimen collection, questionnaires, surgery to remove the tumor from the bladder, and administration of Apalutamide.

Participant Groups

Group I: Arm 1 (apalutamide,TURBT) Experimental Treatment 5 Interventions

Patients receive apalutamide PO 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.

Group II: Arm 2 (placebo, TURBT) Placebo Group 5 Interventions

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.

Apalutamide is already approved in United States, European Union for the following indications:

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

Apalutamide, an androgen receptor inhibitor for high-risk non-metastatic castration-resistant prostate cancer, shows rapid absorption and a large distribution volume, indicating effective body-wide delivery after oral administration.

In a study involving 1092 subjects, the pharmacokinetics of apalutamide and its metabolite were characterized, revealing low inter-individual variability and no significant predictors affecting drug clearance, suggesting consistent dosing effects across different patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. Pérez-Ruixo, C., Pérez-Blanco, JS., Chien, C., et al.[2021]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Interstitial lung disease induced by apalutamide therapy for castration-resistant prostate cancer: A report of a rare case. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Enzalutamide inhibits androgen receptor-positive bladder cancer cell growth. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. [2019]