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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug apalutamide (also known as Erleada) can affect a protein called EGFR, linked to bladder cancer progression. Apalutamide blocks certain hormones to slow or stop cancer cell growth. Participants will receive either apalutamide or a placebo to observe the effects on the protein. The trial seeks men recently diagnosed with non-muscle invasive bladder cancer who have undergone imaging tests showing no signs of advanced cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to early-stage cancer research.

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.

Is there any evidence suggesting that apalutamide is likely to be safe for humans?

Research has shown that apalutamide, a drug that blocks certain hormones, has mostly been studied in prostate cancer. In these studies, patients generally tolerated the treatment well, and serious side effects were rare. For instance, only 0.2% of patients experienced severe issues like a stroke. However, these results come from prostate cancer studies, not bladder cancer, which means bladder cancer patients might react differently to the treatment.

Since apalutamide is in an early stage of testing (phase 1) for bladder cancer, researchers are still collecting safety information specifically for this condition. Phase 1 trials are the first step in clinical testing and mainly focus on safety. While some safety evidence exists from prostate cancer studies, more research is needed to confirm its safety for bladder cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Unlike the standard treatments for bladder cancer, which often include surgery, chemotherapy, and immunotherapy, apalutamide brings a fresh approach by targeting the androgen receptor pathway. Researchers are excited about apalutamide because it is traditionally used in prostate cancer to block hormones that fuel cancer growth, and they believe it might have similar benefits for bladder cancer. This represents a novel mechanism of action for this type of cancer, potentially offering a new line of attack against tumors. The hope is that apalutamide could provide a more targeted and effective treatment option, possibly with fewer side effects compared to existing therapies.

What evidence suggests that apalutamide might be an effective treatment for bladder cancer?

This trial will compare the effects of apalutamide with a placebo in patients undergoing TURBT for bladder cancer. Research has shown that apalutamide can help treat certain types of prostate cancer by blocking male hormones that promote cancer growth. Studies have found that it significantly lowers the risk of cancer spreading and improves survival rates for prostate cancer patients. For bladder cancer, experts believe apalutamide might work by targeting similar growth pathways. Although direct data on its effects in bladder cancer is limited, its known mechanism provides a strong rationale for exploration. Early findings in related cancers suggest that apalutamide could benefit non-muscle invasive bladder cancer by affecting a protein linked to disease progression. ^{1 2 3 6 7}

Who Is on the Research Team?

Edward M Messing

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. innovativemedicine.jnj.com innovativemedicine.jnj.com/us/johnson-johnson-highlights-ambition-transform-treatment-prostate-cancer-and-bladder-cancer-through

Johnson & Johnson Highlights Ambition to Transform the ... Key presentations will include new real-world evidence data adding to the strong and differentiated clinical profile of ERLEADA® (apalutamide) ...

2. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment In the TITAN trial in mHSPC, the combination of APA + ADT reduced the risk of radiographic progression-free survival by 52% (p < 0.001), reduced ...

3. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

4. urotoday.com urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/155493-erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer.html

ERLEADA® (Apalutamide) Demonstrates Statistically ... October 7, 2024; Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months ...

5. urologytimes.com urologytimes.com/view/apalutamide-holds-potential-in-nmibc-expert-says

Apalutamide holds potential in NMIBC, expert says In numerous circumstances, apalutamide, when combined with castrative therapies, makes those castrative therapies more effective. Patients live ...

6. jnjmedicalconnect.com jnjmedicalconnect.com/products/erleada/medical-content/erleada-use-of-erleada-in-high-risk-localized-or-locally-advanced-prostate-cancer

Use of ERLEADA in High-Risk Localized or ... A summary of clinical data regarding ERLEADA® (apalutamide) use in patients with high-risk localized or locally advanced prostate cancer.

7. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.