What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as Difluoromethylornithine (DFMO), High Dose Testosterone, and Enzalutamide, have various side effects. DFMO, which inhibits polyamine synthesis, can cause gastrointestinal disturbances and hearing loss. High Dose Testosterone therapy may lead to cardiovascular issues, erythrocytosis, and exacerbation of pre-existing prostate cancer. Enzalutamide, an androgen receptor inhibitor, commonly causes fatigue, hot flashes, hypertension, and in some cases, seizures. These treatments aim to manage cancer progression but come with significant side effects that need to be monitored.

What prior FDA approvals exist?

Enzalutamide, an androgen receptor inhibitor, has been FDA-approved for both metastatic and non-metastatic castration-resistant prostate cancer (CRPC). Similar drugs like apalutamide and darolutamide, which also inhibit androgen receptor signaling, have been approved for non-metastatic CRPC. High dose testosterone therapy is being explored in clinical trials for its potential to resensitize CRPC to androgen-directed therapies. DFMO, which inhibits ornithine decarboxylase, is not yet FDA-approved for prostate cancer but is under investigation.

What other types of research exist?

Promising novel alternatives for prostate cancer treatment in 2024 include apalutamide, which has shown significant improvement in overall survival and progression-free survival in metastatic castration-sensitive prostate cancer. Additionally, alternative anti-androgen therapies such as flutamide, especially in patients who have relapsed after initial treatment with bicalutamide, may offer benefits. Structured exercise and complementary medicines like American ginseng may also help manage treatment-related side effects and improve quality of life.

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DFMO + Testosterone + Enzalutamide for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments often target the androgen receptor pathway, crucial for prostate cancer cell growth. Difluoromethylornithine (DFMO) inhibits ornithine decarboxylase, reducing polyamine synthesis, which is essential for cell proliferation. High Dose Testosterone activates androgen receptors, paradoxically leading to cancer cell death in certain contexts. Enzalutamide, an androgen receptor inhibitor, blocks the receptor's activation, preventing cancer cell growth. Understanding these mechanisms helps tailor treatments to disrupt cancer cell survival pathways effectively, offering potential for improved patient outcomes.

Phase 2

Recruiting

Led By Laura Sena, MD, PhD

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

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

Must have

Age ≥18 years.

- Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or Prostate Cancer Working Group 3 (PCWG3) for patients with bone disease

Must not have

Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation.

Patients with history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years after end of treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial involves treating patients with advanced prostate cancer that hasn't responded to other treatments. The treatment plan includes taking DFMO, followed by a combination of DFMO and testosterone, and then switching to another medication. These drugs work together to stop cancer cells from growing by blocking important processes they need to survive.

Who is the study for?

Men over 18 with advanced prostate cancer that's resistant to castration and has spread, who have low testosterone levels and disease progression despite previous treatments. They must not be on certain blood thinners or have had major surgery recently, among other criteria.

What is being tested?

The trial tests a combination of DFMO (a drug) and high dose testosterone followed by enzalutamide (another drug) in men with metastatic castrate-resistant prostate cancer. It aims to see if this sequence improves outcomes compared to current treatments.

What are the potential side effects?

Potential side effects may include issues related to hormone therapy such as mood swings, increased red blood cell count, acne or oily skin, mild fluid retention, stimulation of prostate tissue and growth of existing prostate cancer.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My cancer has grown or spread, as shown by recent scans.

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I am sterilized and have documentation proving I have no sperm in my ejaculate.

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I will use protection or abstain if my partner is pregnant or breastfeeding.

Select...

I choose not to have penile-vaginal sex and will continue this choice.

Select...

My testosterone levels are very low (<50 ng/dl).

Select...

My kidney function is good, with a GFR of 50 mL/min/1.73 m2 or higher.

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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 confirmed by a tissue examination.

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I am undergoing hormone therapy for cancer.

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My condition worsened while I was on abiraterone acetate.

Exclusion Criteria

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

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I have not had a blood clot in the past year or am on blood thinners if I did.

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I have a history of seizures or conditions that could lead to seizures.

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I use a catheter for urination due to prostate issues.

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I don't have severe sleep apnea, uncontrolled heart issues, or a high hematocrit level.

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I need help with my daily activities due to my health condition.

Select...

I need opioids to manage my prostate cancer pain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years after end of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years after end of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years after end of treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

PSA response rate at Cycle 1 Day 64

Secondary study objectives

Measurable disease response rate

PSA progression-free survival (PSA-PFS)

PSA response rate at any timepoint

+4 more

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: Repeat Sequential DFMO and High dose Testosterone in Sequence with EnzalutamideExperimental Treatment4 Interventions

Eligible patients will receive 7 days of DFMO (1000 mg PO bid) (days 1-7 of cycle), followed by 56 days of combined testosterone (testosterone cypionate 400 mg IM on day 8 and day 36) and DFMO (1000 mg PO bid) (days 8-63 of cycle), followed by 56 days of enzalutamide (160 mg PO daily) (days 64-119).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enzalutamide

2014

Completed Phase 4

~3820

DFMO

2014

Completed Phase 2

~240

0 / 17Eligibility 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, crucial for prostate cancer cell growth. Difluoromethylornithine (DFMO) inhibits ornithine decarboxylase, reducing polyamine synthesis, which is essential for cell proliferation. High Dose Testosterone activates androgen receptors, paradoxically leading to cancer cell death in certain contexts. Enzalutamide, an androgen receptor inhibitor, blocks the receptor's activation, preventing cancer cell growth. Understanding these mechanisms helps tailor treatments to disrupt cancer cell survival pathways effectively, offering potential for improved patient outcomes.

Prostatic binding protein, polyamine, and DNA synthesis in rat ventral prostate cells.