What side effects are associated with this type of intervention?

Common treatments for prostate cancer, particularly androgen receptor inhibitors like enzalutamide, can have several side effects. Enzalutamide is associated with fatigue, hot flashes, hypertension, and a higher risk of seizures. Other treatments like androgen deprivation therapy (ADT) can cause hot flashes, decreased libido, and osteoporosis. Docetaxel, a chemotherapy agent, often leads to neutropenia, fatigue, and peripheral neuropathy. Bisphosphonates like zoledronic acid, used for bone metastases, can cause osteonecrosis of the jaw and renal toxicity. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several androgen receptor inhibitors for the treatment of prostate cancer, including enzalutamide, apalutamide, and darolutamide. Enzalutamide has been shown to improve overall survival in both metastatic castration-sensitive and castration-resistant prostate cancer. Apalutamide, similar in mechanism to enzalutamide, is approved for nonmetastatic and metastatic castration-sensitive prostate cancer. Darolutamide, with a distinct structure that potentially offers fewer central nervous system side effects, is approved for nonmetastatic castration-resistant prostate cancer. Additionally, abiraterone, an androgen biosynthesis inhibitor, is approved for use in combination with prednisone for metastatic castration-resistant and castration-sensitive prostate cancer.

What other types of research exist?

Promising novel alternatives to Enzalutamide for prostate cancer patients include Apalutamide, which has shown significant improvement in metastasis-free survival in nonmetastatic castration-resistant prostate cancer, and Darolutamide, which has demonstrated efficacy in delaying growth of enzalutamide-resistant prostate cancer, particularly in cells with mutated androgen receptors. Additionally, Lutetium-177-PSMA-617 (Pluvicto) is a novel radioligand therapy that has shown promise in treating metastatic castration-resistant prostate cancer.

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Hormone Therapy

Enzalutamide + Standard Therapy for Prostate Cancer (DIRECT Trial)

Phase 2

Recruiting

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

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

Must have

Histologic diagnosis of prostate adenocarcinoma

Patients decline continuous use of ADT

Must not have

Prior use of salvage systemic therapy

History of malignancy within the past 5 years, excluding non-melanoma skin cancer and in-situ cancer, managed non-curatively

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

This trial is testing if adding enzalutamide, a pill that blocks male hormones, to standard radiation and hormone treatments can improve the quality of life for prostate cancer patients. Participants will receive treatments and be monitored over several months and years to see how they do. Enzalutamide is an antiandrogen used to treat both metastatic and nonmetastatic prostate cancer.

Who is the study for?

Men over 18 with a specific type of prostate cancer that has spread only slightly (oligometastatic) and who haven't had certain other cancers or treatments in the last 5 years. They should be relatively healthy, able to consent, and not on continuous hormone therapy for their cancer.

What is being tested?

The trial is testing if adding a drug called Enzalutamide to standard radiation and hormone therapy improves life quality for men with limited-spread prostate cancer. Participants are randomly chosen to receive either just the standard treatment or the standard plus Enzalutamide for eight months.

What are the potential side effects?

Enzalutamide can cause fatigue, back pain, joint discomfort, hot flushes, diarrhea, and high blood pressure. Radiation may lead to skin irritation at the treated site and fatigue. Hormone therapy might result in hot flashes, sexual dysfunction, and bone thinning.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with prostate cancer.

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I choose not to use hormone therapy continuously.

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I have advanced prostate cancer with 1-10 metastases, diagnosed within the last 6 months.

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I am older than 18 years.

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All my cancer sites can be safely treated with radiation.

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I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

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

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I have had treatment to control cancer after the first treatment failed.

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I haven't had any cancer except for non-melanoma skin cancer or in-situ cancer in the last 5 years.

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I have health issues that make me unsuitable for certain prostate cancer treatments.

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I have been diagnosed with spinal cord compression.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Progression free survival

Secondary study objectives

Patient-reported quality of life

Physician-reported toxicity

Awards & Highlights

No Placebo-Only Group

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm 3 - Study TreatmentExperimental Treatment2 Interventions

Participants in this group will receive standard of care radiation treatment and ADT, plus abiraterone. Participants will start ADT first. Androgen deprivation therapy will be delivered via injection every 4 months as per standard of care (for 8 months total). At the same time, or within 3 months of starting ADT, participants will begin radiation treatment. The radiation treatment course will consist of 2-5 sessions of radiation daily or every other day (the number of sessions will be determined by the physician depending on the location of cancer, number of cancer spots, etc.). In addition, participants will take abiraterone orally (by mouth) daily for 8-9 months. Participants will start the first pill within a month of enrollment. This pill can be taken around the same time of day with or without food.

Group II: Arm 1 - Standard of CareExperimental Treatment1 Intervention

Participants in this group will receive standard of care radiation treatment and ADT. Participants will start ADT first. Androgen deprivation therapy will be delivered via injection every 4 months as per standard of care (for 8 months total). At the same time, or within 3 months of starting ADT, participants will begin radiation treatment. The radiation treatment course will consist of 2-5 sessions of radiation daily or every other day (the number of sessions will be determined by the physician depending on the location of cancer, number of cancer spots, etc.).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enzalutamide

FDA approved

0 / 10Eligibility 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 pathway, which is crucial for the growth of prostate cancer cells. Enzalutamide, a second-generation androgen receptor inhibitor, blocks the binding of androgens to the androgen receptor, inhibits the receptor's nuclear translocation, and prevents its association with DNA, thereby reducing cancer cell proliferation. Abiraterone inhibits CYP17A1, an enzyme critical for androgen production, thus lowering androgen levels. Docetaxel, a chemotherapy agent, disrupts microtubule function, inhibiting cell division. Glucocorticoids are used to manage side effects and enhance the efficacy of other treatments. These mechanisms are vital as they directly interfere with the pathways that prostate cancer cells rely on for growth and survival, offering patients more effective management of their disease.