What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as enzalutamide and high-dose testosterone therapy, have distinct side effect profiles. Enzalutamide can cause fatigue, hot flashes, hypertension, and an increased risk of seizures. High-dose testosterone therapy may lead to fluid retention, gynecomastia, and cardiovascular issues. Combining these treatments aims to disrupt and inhibit androgen receptor signaling, potentially leading to a combination of these side effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of prostate cancer, particularly focusing on androgen receptor signaling pathways. Enzalutamide, a second-generation androgen receptor antagonist, is approved for metastatic castration-resistant prostate cancer (CRPC) and has shown to improve overall survival. Apalutamide, similar to enzalutamide, is also approved for metastatic castration-sensitive prostate cancer (CSPC) and nonmetastatic CRPC, with fewer central nervous system toxicities. Darolutamide, another androgen receptor antagonist, is approved for nonmetastatic CRPC and is noted for its lower risk of central nervous system side effects. These drugs inhibit androgen receptor signaling, which is crucial for prostate cancer cell growth. The combination of high dose testosterone and enzalutamide being studied aims to disrupt and inhibit androgen receptor signaling sequentially to prevent cancer progression.

What other types of research exist?

Promising novel alternatives to High Dose Testosterone and Enzalutamide for prostate cancer patients in 2024 include darolutamide, abiraterone, apalutamide, and docetaxel. These agents have shown significant efficacy in clinical trials and can be considered in combination with androgen deprivation therapy (ADT) for improved outcomes.

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Hormone Therapy

Sequential Testosterone + Enzalutamide for Prostate Cancer

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

Common treatments for prostate cancer include androgen deprivation therapy (ADT), second-generation androgen receptor inhibitors like enzalutamide, and high-dose testosterone therapy. ADT works by reducing androgen levels, which slows the growth of prostate cancer cells. Enzalutamide inhibits androgen receptor signaling, preventing cancer cells from using androgens to grow. High-dose testosterone therapy aims to disrupt androgen receptor signaling, potentially resensitizing cancer cells to further androgen-directed therapies. Understanding these mechanisms is crucial for patients, as it helps tailor treatment plans to effectively manage and potentially overcome resistance in prostate cancer.

Phase 2

Recruiting

Led By Samuel Denmeade, MD

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

Histologically-confirmed adenocarcinoma of the prostate

Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist)

Must not have

Pain due to metastatic prostate cancer requiring treatment intervention with pain medication

Prior chemotherapy with docetaxel or cabazitaxel for castration resistant prostate cancer is prohibited

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if alternating high doses of testosterone and enzalutamide can help men with advanced prostate cancer better than just using enzalutamide alone. It targets men whose cancer has continued to progress despite standard treatments. The treatment works by first disrupting the cancer cells with high-dose testosterone, then blocking any remaining cancer cells from using testosterone with enzalutamide. Enzalutamide has been associated with improved overall survival in men with advanced prostate cancer.

Who is the study for?

Men over 18 with advanced prostate cancer that's worsened despite hormone therapy and possibly one round of chemotherapy. They must have no prior use of certain other cancer drugs, manageable pain levels, and be off steroids for a period. Major organ functions need to be within acceptable ranges, and they should not have had recent major surgery or serious health conditions that could affect their safety.

What is being tested?

The trial is testing if giving high doses of testosterone followed by Enzalutamide can slow down the progression of prostate cancer better than just continuous Enzalutamide. Men will be randomly assigned to either the sequential treatment group or the standard therapy group in an open-label setting.

What are the potential side effects?

Potential side effects may include reactions related to testosterone such as increased red blood cell count, sleep apnea symptoms, heart issues, or liver function changes. Enzalutamide might cause fatigue, back pain, constipation, joint discomfort or hot flushes.

Eligibility Criteria

Inclusion Criteria

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

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My prostate cancer was confirmed through a tissue examination.

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I am undergoing hormone therapy for cancer.

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

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I have not been treated with specific prostate cancer drugs like enzalutamide.

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I am 18 years old or older.

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My cancer progressed despite treatment with abiraterone and hormone therapy.

Exclusion Criteria

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

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I need pain medication for my prostate cancer that has spread.

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I have not received docetaxel or cabazitaxel for prostate cancer.

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I do not have an active, uncontrolled infection or a known history of HIV/AIDS or hepatitis B or C.

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

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

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I have never been treated with enzalutamide.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

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

Clinical or Radiographic Progression free survival

Secondary study objectives

Objective Response Rate as Determined by RECIST

Prostate-Specific Antigen Response Rate

Quality of Life as Assessed by FACIT Fatigue Scale

+4 more

Side effects data

From 2017 Phase 3 trial • 92 Patients • NCT01275365

18%

Back pain

18%

Upper respiratory tract infection

Diarrhoea

Arthralgia

Dental caries

Muscle spasms

Nasopharyngitis

Musculoskeletal stiffness

Ifluenza

Pain in extremity

Ear discomfort

Cataract operation

Palpitations

Gastrooesophageal reflux disease

Oropharyngeal pain

Nocturia

Polyuria

Prostatic asymmetry

Asthma

Polycythaemia

Constipation

Tooth loss

Fatigue

Bronchitis

Contusion

Fall

Laceration

Tendon injury

Biopsy skin

Prostatic specific antigen abnormal

Myalgia

Lower urinary tract symptoms

Urine flow decreased

Rash macular

Noninfective gingivitis

Inflammation

Oedema peripheral

Muscle strain

Gait disturbance

Nasal congestion

Limb injury

Acne

100%

80%

60%

40%

20%

Study treatment Arm

Placebo/Low Protein

Placebo/High Protein

Testosterone/Low Protein

Testosterone/High Protein

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C: Variable Sequential Testosterone and EnzalutamideExperimental Treatment3 Interventions

Patients in Arm C will receive intramuscular injection with testosterone cypionate (T) at a dose of 400 mg every 28 days x 2 injections per cycle. Each cycle is 56 days. Patients with PSA progression will stop T injection and begin Enzalutamide. Patients on T with initial PSA decline will remain on high dose T for additional cycles of 2 injections until PSA progression occurs (≥25% increase in PSA from PSA nadir on current BAT cycle). These patients will then be started on Enzalutamide. Patients with PSA progression will stop Enzalutamide and will restart injections of T with 2 injections/cycle. Patients on enzalutamide with initial PSA decline after one 56-day cycle will continue on Enzalutamide until PSA progression occurs (≥25% increase in PSA from PSA nadir on current Enzalutamide cycle). These cycles of switching between T and Enza with onset of PSA progression will continue until clinical and/or radiographic progression occurs.

Group II: Arm B: Sequential Testosterone and EnzalutamideExperimental Treatment3 Interventions

Patients in Arm B will receive intramuscular injection with testosterone cypionate (T) at a dose of 400 mg every 28 days x 2 (i.e. cycle 1). On Day 1 of cycle 2, patients will stop testosterone and begin enzalutamide 160 mg po q day for 56 days. Each cycle is 56 days. On Day 1 of cycle 3, patient will not take enzalutamide and will again receive injection of testosterone. Patients will continue to alternate one cycle of testosterone (2 injections) with one cycle of 56 days of enzalutamide.

Group III: Arm A: EnzalutamideExperimental Treatment1 Intervention

Patients randomized to Arm A will receive continuous therapy with standard dose Enzalutamide (160 mg oral daily).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enzalutamide

2014

Completed Phase 4

~3820

Testosterone enanthate

2014

Completed Phase 3

~190

Testosterone cypionate

2014

Completed Phase 2

~440

0 / 14Eligibility 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

Common treatments for prostate cancer include androgen deprivation therapy (ADT), second-generation androgen receptor inhibitors like enzalutamide, and high-dose testosterone therapy. ADT works by reducing androgen levels, which slows the growth of prostate cancer cells. Enzalutamide inhibits androgen receptor signaling, preventing cancer cells from using androgens to grow. High-dose testosterone therapy aims to disrupt androgen receptor signaling, potentially resensitizing cancer cells to further androgen-directed therapies. Understanding these mechanisms is crucial for patients, as it helps tailor treatment plans to effectively manage and potentially overcome resistance in prostate cancer.

A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer.