Safety and Efficacy of Oral Testosterone Undecanoate Followed by Enzalutamide as Therapy for Men With Metastatic Castrate Resistant Prostate Cancer

NCT05081193 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: J2178IRB00284702
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Previous studies of high dose testosterone therapy given intramuscularly to men with metastatic castrate resistant prostate cancer suggest that high serum levels of testosterone may be required for clinical response. This injection regimen was given as one dose of 400mg injection every 28 days, which initially produces high serum testosterone levels but these levels drop to a varying degree in some men over the 28-day cycle. In this 30 patient trial will analyze the effects of oral testosterone therapy in men with metastatic castrate resistant prostate cancer taken on a schedule of seven days of oral testosterone therapy followed by seven days of no therapy for a twenty-eight day cycle. This therapy will be given for three 28 day cycles consecutively followed by radiographic scans to evaluate the metastatic disease. Patients will be allowed to continue on this therapy until the patients show signs of radiographic progression. If the patients show signs of radiographic progression after the first three cycles, the patients will stop taking the oral testosterone therapy and begin taking enzalutamide therapy. Enzalutamide therapy will be taken for three 28 day cycles, then radiographic scans will be taken. If there are no signs of radiographic progression, patients can continue to take enzalutamide therapy for an additional 3 cycles while on study. Patients with continued PSA or objective response will come off study but continue on enzalutamide as standard of care therapy. This study will help the investigators to understand if treating these men with the highest FDA approved dose of oral testosterone therapy will achieve similar and sustained high levels of serum testosterone that will produce similar or enhanced therapeutic response to the therapy when compared to the serum testosterone levels found in the previous injection therapy trials.

Conditions

Prostate Cancer; Castration-resistant Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Keywords

Oral Testosterone Therapy; Enzalutamide

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate of Oral Testosterone Undecanoate (CT Scan)

  Radiographic responses to Oral Testosterone therapy using CT scan measurements. Radiographic progression is assessed by RECIST (Response Evaluation Criteria in Solid Tumors). Per RECIST, progression is defined as ≥ 20% and ≥ 5 mm from nadir of the sum of the diameters of target lesions.

  Up to 2 years

Secondary Outcomes (14)

• PSA50 Response to Oral Testosterone Therapy

  2 years

• Time to PSA Progression While on Oral Testosterone

  Up to 2 years

• Time to Clinical or Radiographic Progression While on Oral Testosterone

  Up to 2 years

• PSA50 Response to Enzalutamide Therapy

  2 years

• Objective Response Rate of Enzalutamide Therapy (CT Scan)

  2 years

Study Arms (1)

Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide Therapy

EXPERIMENTAL

Oral Testosterone Therapy-396 mg given twice per day on days 1-7 and 15-21 of a 28 day cycle until radiographic progression. After a 21 day washout period, Enzalutamide therapy given at 160 mg once daily will be taken for a maximum of 6 cycles while on study.

Drug: Testosterone Undecanoate; Drug: Enzalutamide

Interventions

Testosterone Undecanoate DRUG

198mg taken twice daily

Also known as: Jatenzo

Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide Therapy

Enzalutamide DRUG

160mg taken once daily

Also known as: Xtandi

Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has the ability to understand and willingness to sign a written informed consent document.
• Patient is a male aged 18 years or older.
• Patient has histologically-confirmed adenocarcinoma of the prostate
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 (as defined in Appendix A: Performance Status Criteria;
• Patient has evidence of metastatic, measurable disease by CT scan. Measurable disease is defined by RECIST 1.1 as at least one measurable lesion ≥10mm by CT scan
• Patient is progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist)
• Patient has documented castrate level of serum testosterone (\<50 ng/dl)
• Patient is progressing on luteinizing hormone-releasing hormone (LHRH) agonist/antagonist plus anti-androgen or abiraterone for CSPC. (Note: Must be off anti-androgen or abiraterone for 4 weeks prior to first treatment with OT.) LHRH (luteinizing hormone-releasing hormone)
• Patient has had prior docetaxel for CSPC. Note: Docetaxel is permitted if ≤ 6 doses were given in conjunction with first-line androgen deprivation therapy and \>6 months since last dose of docetaxel. (CSPC-castrate sensitive prostate cancer)
• Patient is currently taking prednisone and cannot be weaned entirely off. Note: Patient's dose must be maintained on lowest stable dose that relieves symptoms. Patient is receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone if possible prior to starting OT.
• Patient has had a rising PSA on two successive measurements at least two weeks apart.
• Patient agrees to continue on castrating therapy throughout OT treatment.
• Patient's screening lab values are within the following parameters:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
• Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)

You may not qualify if:

• Patient has pain due to metastatic prostate cancer requiring opioid analgesics.
• Patient has had prior treatment with any agent for metastatic castration-resistant prostate cancer. (Includes docetaxel, cabazitaxel, anti-androgen, abiraterone, or investigational agents)
• Patient requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia. Note: Patients with indwelling catheter/suprapubic catheter to relieve obstruction are eligible.
• Patient has 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, epidural spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction).
• Patient has 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, epidural spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction).
• Patient has active uncontrolled infection, such as HIV/AIDS or chronic hepatitis B or untreated chronic hepatitis C.
• Patient has had prior history of a thromboembolic event within the past two years and not currently on systemic anticoagulation.
• Patient is on Coumadin. Note: If anticoagulation therapy is mandatory, patient must be switched to an alternative medication) Patients receiving anticoagulation therapy with warfarin, rivaroxaban or apixaban are not eligible for study. \[Patients on enoxaparin or edoxaban are eligible for study. Patients on warfarin, rivaroxaban or apixaban, who can be transitioned to enoxaparin prior to starting study treatments, will be eligible.
• Patient has hematocrit \>50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure \[per Endocrine Society Clinical Practice Guidelines\].

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Clarus Therapeutics, Inc.: collaborator
• Allegheny Health Network: collaborator

Study Sites (2)

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

testosterone undecanoate; Testosterone Propionate; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Samuel Denmeade, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Oral Testosterone Therapy-396 mg given twice per day on days 1-7 and 15-21 of a 28 day cycle until radiographic progression. After a 21 day washout period, Enzalutamide therapy given at 160 mg once daily will be taken for a maximum of 6 cycles while on study.

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: October 18, 2021
• Study Start: March 7, 2022
• Primary Completion: August 4, 2025
• Study Completion: August 4, 2025
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

US (2)