Sequential Testosterone and Enzalutamide Prevents Unfavorable Progression

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to 90 Years
• SexMale
• Healthy volunteersNo

You may be able to join if

• ECOG Performance status ≤2.
• Age ≥18 years.
• Histologically-confirmed adenocarcinoma of the prostate.
• Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist).
• Documented castrate level of serum testosterone (<50 ng/dl).
• Metastatic disease radiographically documented by CT or bone scan.
• Must have had disease progression while on combination of abiraterone acetate plus ADT either given concurrently or sequentially based on:
• PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart And/ Or
• Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or PCWG3 for patients with bone disease
• Screening PSA must be ≥ 1.0 ng/mL.
• Patients with soft tissue lesion amenable to biopsy must agree to biopsy collection pre-treatment and at a defined point on treatment to perform tumor tissue analysis.
• No prior treatment with enzalutamide, apalutamide, darolutamide, or other investigational AR targeted treatment is allowed.
• Prior treatment with testosterone is allowed.
• Prior treatment with one chemotherapy regimen with docetaxel (≤ 6 doses) for hormonesensitive prostate cancer is allowed.
• Prior treatment with Provenge vaccine and 223Radium (Xofigo) is allowed if >4 weeks from last dose.
• Patients must be withdrawn from abiraterone for ≥ 2 weeks.
• Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period.
• Acceptable liver function:
• Bilirubin < 2.5 times institutional upper limit of normal (ULN)
• AST (SGOT) and ALT (SGPT) < 2.5 times ULN
• Acceptable renal function:
• a. Serum creatinine < 2.5 times ULN
• Acceptable hematologic status:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
• Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
• Hemoglobin ≥ 8 g/dL.
• At least 4 weeks since prior radiation or chemotherapy.
• Ability to understand and willingness to sign a written informed consent document.

You cannot join if

• Pain due to metastatic prostate cancer requiring treatment intervention with pain medication.
• ECOG Performance status ≥3
• Prior treatment with enzalutamide is prohibited.
• Prior chemotherapy with docetaxel or cabazitaxel for castration resistant prostate cancer is prohibited.
• Requires urinary self-catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH). Patients with indwelling Foley or suprapubic catheter for obstructive symptoms are eligible.
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, extensive liver metastases).
• Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.
• Active uncontrolled infection, including known history of HIV/AIDS or hepatitis B or C.
• Any condition or mental impairment that may compromise the ability to give informed consent, patient's safety or compliance with study requirements as determined by the investigator.
• Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. [Patients on enoxaparin eligible for study. Patients on warfarin, rivaroxaban,or apixaban, who can be transitioned to enoxaparin prior to starting study treatments will be eligible].
• Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation.
• Hematocrit >51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (34)]
• Patients allergic to sesame seed oil or cottonseed oil are excluded.
• Major surgery (eg, requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (ie, unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

deuterated enzalutamide. A deuterated form of enzalutamide, an orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Upon administration, deuterated enzalutamide competitively binds to and inhibits the activity of ARs expressed on prostate cancer cells, which impairs nuclear translocation and DNA binding, resulting in apoptosis of prostate cancer cells. This results in a reduction in prostate cancer cell growth. AR overexpression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance. Deuterium incorporation, by replacing the hydrogen atoms of the N-CH3 moiety with deuterium atoms, decreases enzalutamide's metabolism and allows for an increased pharmacokinetic profile, thereby enhancing its anti-tumor efficacy compared to non-deuterated enzalutamide. As the deuterated form can’t cross the blood-brain barrier (BBB), the deuterated form also reduces the unwanted brain-related side effects of enzalutamide and improves its safety profile. NCI Drug Dictionary

Treatments listed in the registry

• Testosterone cypionate (Drug): Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.
• Enzalutamide (Drug): Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.
• Testosterone enanthate (Drug): Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• CT scans: Part of the study plan
• bone scan: Part of the study plan

Main goals

• Clinical or Radiographic Progression free survival (Up to 2 years)

Other goals

• Safety of cyclical parenteral testosterone as assessed by the revised National Cancer Institute Common Toxicity Criteria
• Prostate-Specific Antigen Response Rate
• Objective Response Rate as Determined by RECIST
• Quality of Life as Assessed by FACIT Fatigue Scale
• Quality of Life as Assessed by Short Form 36
• Time to Overall Survival
• Radiographic Progression free survival

Planned enrollment: 150 (estimated).

• University of California, San Diego (UCSD), San Diego, California
• Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland
• Dana-Faber Cancer Institute, Boston, Massachusetts
• University of Minnesota, Minneapolis, Minnesota
• University of Nebraska Medical Center, Omaha, Nebraska
• University of Washington/Fred Hutchinson Cancer Center, Seattle, Washington

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT04363164
• NCI Drug Dictionary: C71744

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jul 16, 2026. Public record; not medical advice.