Sequential Testosterone and Enzalutamide Prevents Unfavorable Progression
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|ClinicalTrials.gov Identifier: NCT04363164|
Recruitment Status : Active, not recruiting
First Posted : April 27, 2020
Last Update Posted : September 2, 2020
|Condition or disease||Intervention/treatment||Phase|
|Castration Resistant Metastatic Prostate Cancer||Drug: Testosterone cypionate Drug: Enzalutamide Drug: Testosterone enanthate||Phase 2|
Eligible patients are those who have progressive disease after treatment with Abi either in combination with ADT as initial therapy or as second-line therapy after development of resistance to primary ADT. Patients will continue on ADT with Luteinizing hormone-releasing hormone (LHRH) agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonist (Degarelix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production. Patients will be randomized 1:2 and stratified based on whether patients received Abi in combination with ADT or in sequence after progression on ADT and based on duration of response to Abi (<6 or ≥ 6 months). Patients randomized to Arm A will receive continuous therapy with standard dose Enza (160 mg po q day). Patients randomized to Arm B will receive Sequential Testosterone and Enzalutamide (STE). 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). This dose was selected based on data demonstrating that it produces an initial high dose serum level of T (i.e. > 1500 ng/dL or 3-10 times normal level) with eugonadal levels achieved at the end of two weeks and near castrate levels after 28 days. 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.
Patients will have prostate-specific antigen (PSA) level and symptoms assessment checked every cycle. Every 2 cycles (~4 months) patients will have repeat bone/CT scans to evaluate treatment response status. On CT scan, radiographic progression will be defined by RECIST criteria (i.e. >20% increase in the sum of target lesions). On bone scan, radiographic progression will be defined by PCWG3 criteria as ≥ 2 new bone lesions.
Patients with PSA progression but with disease response or stable disease on imaging studies will remain on study until clinical or radiographic progression criteria are met. Patients with radiographic disease progression will stop treatment and come off study. Patients with clinical progression due to pain flare after first two injection of testosterone can remain on study. If pain persists after first cycle of enzalutamide, patients will stop treatment and come off study. If pain resolves on enzalutamide, but returns with next or subsequent cycles of testosterone, patients will stop treatment and come off study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Study Comparing Sequential High Dose Testosterone and Enzalutamide to Enzalutamide Alone in Asymptomatic Men With Castration Resistant Metastatic Prostate Cancer|
|Actual Study Start Date :||August 19, 2020|
|Estimated Primary Completion Date :||July 2025|
|Estimated Study Completion Date :||July 2026|
Experimental: Arm A: Enzalutamide
Patients randomized to Arm A will receive continuous therapy with standard dose Enzalutamide (160 mg oral daily).
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.
Other Name: Cytoxan
Experimental: Arm B: Testosterone cypionate or Testosterone enanthate
Patients randomized to Arm B will receive intramuscular injection with testosterone cypionate or testosterone enanthate at a dose of 400 mg every 56 days
Drug: Testosterone cypionate
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.
Other Name: Depo-Testosterone Injection
Drug: Testosterone enanthate
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.
Other Name: Delatestryl
- Clinical or Radiographic Progression free survival [ Time Frame: Up to 2 years ]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.
- Safety of cyclical parenteral testosterone as assessed by the revised National Cancer Institute Common Toxicity Criteria [ Time Frame: Up to 2 years ]Safety of cyclical parenteral testosterone in asymptomatic men with recurrent castrate resistant prostate cancer. Safety will be evaluated by adverse events as assessed by the revised National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.0
- Prostate-Specific Antigen Response Rate [ Time Frame: Up to 2 years ]Number of participants achieving a Prostate-Specific Antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria.
- Objective Response Rate as Determined by RECIST [ Time Frame: Up to 2 years ]Number of participants with partial (PR) or complete response (CR) as defined by response evaluation criteria in solid tumors (RECIST), where CR is a disappearance of all target lesions and PR is ≥30% reduction in the sum of the longest diameter of target lesions.
- Quality of Life as Assessed by FACIT Fatigue Scale [ Time Frame: Up to 1 year ]The Functional Assessment of Chronic Illness Therapy - Fatigue has a score range of 0-52 with higher scores indicating better quality of life.
- Quality of Life as Assessed by Short Form 36 [ Time Frame: Up to 1 year ]All questions are scored on a scale from 0 to 100. The total score from all of the questions answered is divided by the total number of the questions answered yielding a global score from 0-100 with 100 representing the highest level of functioning possible.
- Time to Overall Survival [ Time Frame: Up to 3 years ]Time to overall survival will be calculated as months from date of off treatment up to 3 years.
- Radiographic Progression free survival [ Time Frame: Up to 2 years ]Number of months until 20% increase in the sum of target lesions on CT scans or greater than 2 new bone lesions on bone scan.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04363164
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Samuel Denmeade, MD||SKCCC at Johns Hopkins|