Sequential Testosterone and Enzalutamide Prevents Unfavorable Progression

NCT04363164 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J2060sIRBIRB00312725
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 6

Brief Summary

Asymptomatic men without pain due to prostate cancer progressing with metastatic CRPC after treatment with combination or sequential ADT + Abi will be treated on a randomized, open label study to determine if sequential treatment with high dose T and Enza will improve primary and secondary objectives vs. continuous Enza as standard therapy.

Conditions

Castration Resistant Metastatic Prostate Cancer

Keywords

Testosterone; Enzalutamide; Androgen Deprivation Therapy (ADT)

Outcome Measures

Primary Outcomes (1)

• Clinical or Radiographic Progression free survival

  Time from the date of the randomization to the date of first documented radiological progression per RECIST 1.1 for soft tissue or PCWG3 for bone lesions, or clinical progression or death, whichever occurs first.

  Up to 2 years

Secondary Outcomes (7)

• Safety of cyclical parenteral testosterone as assessed by the revised National Cancer Institute Common Toxicity Criteria

  Up to 2 years

• Prostate-Specific Antigen Response Rate

  Up to 2 years

• Objective Response Rate as Determined by RECIST

  Up to 2 years

• Quality of Life as Assessed by FACIT Fatigue Scale

  Up to 1 year

• Quality of Life as Assessed by Short Form 36

  Up to 1 year

Study Arms (3)

Arm A: Enzalutamide

EXPERIMENTAL

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

Drug: Enzalutamide

Arm B: Sequential Testosterone and Enzalutamide

EXPERIMENTAL

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.

Drug: Testosterone cypionate; Drug: Enzalutamide; Drug: Testosterone enanthate

Arm C: Variable Sequential Testosterone and Enzalutamide

EXPERIMENTAL

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.

Drug: Testosterone cypionate; Drug: Enzalutamide; Drug: Testosterone enanthate

Interventions

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.

Also known as: Depo-Testosterone Injection

Arm B: Sequential Testosterone and Enzalutamide; Arm C: Variable Sequential Testosterone and Enzalutamide

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.

Arm A: Enzalutamide; Arm B: Sequential Testosterone and Enzalutamide; Arm C: Variable Sequential Testosterone and Enzalutamide

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.

Also known as: Delatestryl

Arm B: Sequential Testosterone and Enzalutamide; Arm C: Variable Sequential Testosterone and Enzalutamide

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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.

You may not qualify 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• United States Department of Defense: collaborator

Study Sites (6)

University of California, San Diego (UCSD)

San Diego, California, 92037, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Dana-Faber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

University of Washington/Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

testosterone 17 beta-cypionate; enzalutamide; testosterone enanthate

Study Officials

• Samuel Denmeade, MD

  SKCCC at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

GU oncology

CONTACT

4109551239; ProstateCancerClinicalTrials@live.johnshopkins.edu

Harry Cao, MA

CONTACT

443-287-6882; hcao7@jhmi.edu

Study Design

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

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: August 19, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)