Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance (Transformer)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02286921|
Recruitment Status : Active, not recruiting
First Posted : November 10, 2014
Results First Posted : May 1, 2019
Last Update Posted : October 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Castration Resistant Metastatic Prostate Cancer||Drug: Testosterone cypionate Drug: Enzalutamide Drug: Testosterone Enanthate||Phase 2|
Eligible patients will have metastatic CRPC with no disease related symptoms and progression on Androgen deprivation therapy and will have progressed post-treatment with abiraterone. Patients will continue on Androgen deprivation therapy with Luteinising Hormone Releasing Hormone agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) or Luteinising Hormone Releasing Hormone antagonist (Degarelix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production. Patients will be randomized 1:1 and stratified based on duration of prior abiraterone acetate therapy (6 months or less or greater than 6 months). Patients randomized to BAT (Arm A) will receive intramuscular injections with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dose was selected based on data demonstrating that it produces an initial supraphysiologic 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. Patients randomized to enzalutamide (Arm B) will receive daily oral dose of 160 mg. Each cycle is defined as 28 days.
Patients will have Prostate-specific antigen level and symptoms assessment checked every cycle. Every 3 cycles 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 PCWG2 criteria as ≥ 2 new bone lesions. However, for the first reassessment scan only, patients should remain on study and have a confirmatory scan performed 12 weeks (3 cycles) later. If this confirmatory scan shows 2 or more additional new lesions, this defines progression. The date of progression is the date of the first reassessment bone scan. If the confirmatory scan does not show any additional new lesions, patient remains on study. If progression is observed on subsequent bone scans, a confirmatory scan is not required; the date of this bone scan is the date of progression.
Patients with Prostate-specific antigen progression but with disease response or stable disease on imaging studies will remain on study until radiographic or other clinical progression criteria are met. Patients with radiographic disease progression will not receive continued BAT (arm A) or enzalutamide (arm B) and will be eligible for crossover to the opposite therapy. Patients on the BAT arm A can cross over to receive enzalutamide at time of progression or can choose to go off study and be treated with other standard of care treatments. Patients on the enzalutamide arm B will be allowed to cross-over to receive BAT or can choose to go off study and be treated with other standard of care treatments.
Patients with clinical progression due to prostate cancer must meet study exclusion criteria to be permitted to cross-over to the opposite treatment. Patients with clinical progression due to pain from prostate cancer are not permitted to cross-over.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||222 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II Study Comparing Bipolar Androgen Therapy vs. Enzalutamide in Asymptomatic Men With Castration Resistant Metastatic Prostate Cancer|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||October 26, 2018|
|Estimated Study Completion Date :||November 22, 2019|
Experimental: Arm A: Testosterone cypionate or testosterone enanthate
Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 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
Experimental: Arm B: Enzalutamide
Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle.
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: Xtandi
- Progression Free Survival as Measured by Number of Months Until Clinical or Radiographic Progression [ Time Frame: up to 2 years ]
Time to clinical progression will be defined as months from randomization to any of the following (whichever occurs earlier):
- Cancer pain requiring initiation of chronic administration of opiate analgesia (oral opiate use for ≥3 weeks; parenteral opiate use for ≥7 days. Patients with cancer pain requiring opiate analgesia for relief should also be assessed by the investigator for the need for initiating systemic chemotherapy or palliative radiation.
- Development of a skeletal-related event (SRE): pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone.
- Development of clinically significant symptoms due to loco-regional tumor progression (e.g. urinary obstruction) requiring surgical intervention or radiation therapy.
- Radiographic Progression [ Time Frame: up to 2 years ]Number of months until 20% increase in the sum of target lesions on CT scans.
- 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.
- Time to Prostate-Specific Antigen Progression [ Time Frame: Up to 2 years ]Reported as number of months till Prostate-Specific Antigen increase of greater or equal to 50% according to Prostate Cancer Working Group (PCWG2) criteria.
- Quality of Life as Assessed by the Positive Affect Score of the Positive and Negative Affect Schedule (PANAS) [ Time Frame: up to 1 year ]The Positive Affect Score is calculated by adding the scores on items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores can range from 10 - 50, with higher scores representing higher levels of positive affect.
- Quality of Life as Assessed by the Negative Affect Score of the Positive and Negative Affect Schedule (PANAS) [ Time Frame: up to 1 year ]The Negative Affect Score is calculated by adding the scores on items 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.
- Change in Quality of Life as Assessed by the International Index of Erectile Function (IIEF) Questionnaire [ Time Frame: up to 1 year ]The IIEF assesses erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), orgasmic satisfaction (OS). Each of domains are scored on a scale of 0 to 5 with a lower score indicating a bad quality sex life. The IIEF questionnaire has a total score that ranges from 5 to 25 with lower score indicating less erectile dysfunction. A positive change in the score reflects better outcome.
- 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.
- 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.
- Pain Severity as Assessed by the Brief Pain Inventory [ Time Frame: 1 year ]Severity is calculated by adding the scores for questions 2, 3, 4 and 5 and then dividing by 4. This gives a severity score out of 10, high score indicates more severe pain.
- Pain Interference as Assessed by the Brief Pain Inventory [ Time Frame: 1 year ]Interference is calculated by adding the scores for questions 8a, b, c, d, e, f and g and then dividing by 7. This gives an interference score out of 10, higher score indicates more pain interference.
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): NCT02286921
|Principal Investigator:||Samuel Denmeade, MD||Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center|