What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as androgen receptor inhibitors like enzalutamide, can cause side effects including fatigue, seizures, hypertension, and cognitive impairment. Anti-inflammatory agents like indomethacin may lead to gastrointestinal issues, renal impairment, and cardiovascular risks. When these treatments are combined, patients may experience an additive side effect profile, requiring careful monitoring by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several androgen receptor inhibitors for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including enzalutamide, apalutamide, and darolutamide. These drugs block the androgen receptor signaling pathway, which is essential for prostate cancer cell growth. Abiraterone, another approved drug, inhibits androgen production and is used in mCRPC treatment. While indomethacin, an anti-inflammatory drug, is being studied in combination with enzalutamide, its role in prostate cancer treatment is not yet established.

What other types of research exist?

Promising novel alternatives to Enzalutamide and Indomethacin for prostate cancer patients in 2024 include Apalutamide, which has shown significant improvement in metastasis-free survival in nonmetastatic CRPC, and immunotherapies such as Pembrolizumab and Atezolizumab, which are being investigated for their efficacy in metastatic CRPC. Additionally, Lutetium-177-PSMA-617, a radioligand therapy, has shown promise in treating metastatic CRPC.

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Antiandrogen

Enzalutamide + Indomethacin for Prostate Cancer

Phase 1 & 2

Recruiting

Led By Chong-Xian Pan

Research Sponsored by Mamta Parikh

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable): Progression of unidimensionally measurable disease, progression of evaluable but not measurable disease, rising PSA

Must not have

Patients with an active bleeding diathesis

HIV-positive patients on combination antiretroviral therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the effects of enzalutamide and indomethacin in treating prostate cancer that doesn't respond to hormone treatments, has returned, or has spread. Enzalutamide blocks male hormones that help cancer grow, while indomethacin reduces inflammation and may also fight cancer. The goal is to see if this combination can reduce cancer markers and improve patient outcomes.

Who is the study for?

Men with hormone-resistant prostate cancer that has returned or spread, who have tried castration (surgery or drugs) and still show signs of the disease. They must be in fairly good health otherwise, with a life expectancy over 6 months, normal organ function tests, and agree to use contraception. Those with other recent cancers, brain metastases, certain infections like HIV on treatment, uncontrolled illnesses, history of seizures or severe gastrointestinal issues are not eligible.

What is being tested?

The trial is testing how well enzalutamide combined with indomethacin works for treating advanced prostate cancer resistant to hormonal therapy. Enzalutamide lowers androgen levels/block its use by tumors; indomethacin is added to see if it enhances this effect. It's a phase I/II study which means they're looking at safety as well as effectiveness.

What are the potential side effects?

Possible side effects include allergic reactions similar to those from compounds related to enzalutamide or indomethacin. There may also be risks of heart problems due to pre-existing conditions being exacerbated by the medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself but might not be able to do heavy physical work.

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My prostate cancer is resistant to hormone therapy.

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My PSA level is 5.0 or higher, and I have no signs of cancer spread.

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I have confirmed prostate cancer, which may be recurrent or has spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a condition that causes me to bleed easily.

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I am HIV-positive and on antiretroviral therapy.

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I have brain metastases.

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I am allergic to medications similar to enzalutamide or indomethacin.

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I have had peptic ulcers or bleeding in my stomach/intestines before.

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I do not have any unmanaged ongoing illnesses.

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I have a digestive system condition.

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I have been treated with enzalutamide or ketoconazole for prostate cancer.

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I am using herbal or alternative medicines for prostate cancer.

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I have prostate cancer that has spread and is causing symptoms.

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I have a history of seizures or brain-related health issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

PSA response rate defined as >= 50% decrease from the baseline

Secondary study objectives

Overall survival

PFS

Side effects data

From 2014 Phase 4 trial • 270 Patients • NCT01957215

Vascular rupture

Drug eruption

Gingival bleeding

Application site pruritis

Inflammation

Upper respiratory tract infections

Nasopharyngitis

Ligament sprain

Pruritis

Rash

100%

80%

60%

40%

20%

Study treatment Arm

Indomethacin Patch

Placebo Patch

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (enzalutamide, indomethacin)Experimental Treatment2 Interventions

Patients receive enzalutamide PO QD and indomethacin PO BID or QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enzalutamide

2014

Completed Phase 4

~3820

Indomethacin

2011

Completed Phase 4

~5790

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target the androgen receptor signaling pathway, which is crucial for the growth and survival of prostate cancer cells. Enzalutamide, a second-generation androgen receptor inhibitor, works by blocking the binding of androgens to the androgen receptor, inhibiting the receptor's nuclear translocation, and preventing its association with DNA, thereby reducing cancer cell proliferation. Indomethacin, an anti-inflammatory agent, may help by reducing inflammation, which can contribute to cancer progression. These mechanisms are vital for prostate cancer patients as they directly interfere with the cancer's ability to grow and spread, offering a targeted approach to manage the disease effectively.

Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Hirmand M, Smith MR. Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: bertrand.tombal@uclouvain.be. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14].