RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistance (The RESTORE Study) (Restore)
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|ClinicalTrials.gov Identifier: NCT02090114|
Recruitment Status : Active, not recruiting
First Posted : March 18, 2014
Last Update Posted : November 17, 2021
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Testosterone cypionate Drug: Testosterone Enanthate Drug: Abiraterone acetate (Cohort B = CLOSED TO ACCRUAL) Drug: Enzalutamide (Cohort A = CLOSED TO ACCRUAL)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study to Determine Sequential Response to Bipolar Androgen Therapy (BAT) Followed by Enzalutamide or Abiraterone Post-BAT in Men With Prostate Cancer Progressing on Combined Androgen Ablative Therapies|
|Study Start Date :||June 2014|
|Estimated Primary Completion Date :||April 2022|
|Estimated Study Completion Date :||April 2023|
Experimental: Post-abiraterone or post-enzalutamide or post-castration only
Men with castration-resistant prostate cancer who have progressed on either abiraterone or enzalutamide or castration-only therapy will be enrolled to this arm. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with either abiraterone 1000 mg by mouth daily or enzalutamide 160 mg by mouth daily, depending on which drug they previously received or remain on LHRH agonist alone for one month to re-establish a castrate level of testosterone (<50 ng/dL).
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
Drug: Abiraterone acetate (Cohort B = CLOSED TO ACCRUAL)
Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate.
Other Name: Zytiga
Drug: Enzalutamide (Cohort A = CLOSED TO ACCRUAL)
XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides.
Other Name: Xtandi
- Prostate Specific Antigen (PSA) response to Bipolar Androgen Therapy (BAT) [ Time Frame: up to 18 months ]Number of participants with ≥50% PSA reduction from pre-BAT baseline level
- PSA response to enzalutamide or abiraterone acetate post Bipolar Androgen Therapy [ Time Frame: up to 24 months ]Number of participants with ≥50% PSA reduction after enzalutamide or abiraterone acetate post-BAT from baseline
- PSA response to castrate levels of testosterone post Bipolar Androgen Therapy [ Time Frame: up to 18 months ]Number of participants who return to castrate levels of testosterone post Bipolar Androgen Therapy
- PSA progression on enzalutamide or abiraterone acetate or castrate levels post-BAT [ Time Frame: up to 18 months ]Time to PSA progression on enzalutamide or abiraterone acetate or return to castrate levels of testosterone post-BAT
- PSA progression on BAT (Bipolar Androgen Therapy ) [ Time Frame: up to 18 months ]Time to PSA progression on BAT
- Disease response as defined by RECIST 1.1 (soft tissue lesions) and PCWG2 criteria (bone lesions) [ Time Frame: up to 18 months ]Number of participants with complete or partial response post-BAT and post-treatment with enzalutamide or abiraterone acetate as defined by RECIST 1.1 (for soft tissue lesions) and PCWG2 criteria (for bone disease), or return to castration-only post-BAT.
- Initiation of docetaxel chemotherapy [ Time Frame: up to 18 months ]Time to initiation of docetaxel chemotherapy
- Quality of Life (QoL) as assessed by FACIT-F score [ Time Frame: Change from baseline to 18 months ]Functional Assessment of Chronic Illness Therapy, Fatigue Subscale (FACIT-F) assesses Fatigue with a total score range of 0-52, with a higher score reflecting better QoL.
- Safety and Tolerability as assessed by Number of Participants with Adverse Events [ Time Frame: 18 months ]Number of participants who experience adverse events, as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
- Fasting glucose [ Time Frame: 18 months ]Fasting blood glucose level (mg/dL)
- Hemoglobin A1c [ Time Frame: 18 months ]Serum percent glycosylated hemoglobin (Hemoglobin A1C)
- Fasting insulin [ Time Frame: 18 months ]Fasting insulin levels
- Serum C-telopeptide [ Time Frame: 18 months ]Serum C-telopeptide levels (pg/mL)
- Osteocalcin [ Time Frame: On average at 18 months ]Serum Osteocalcin levels (ng/mL)
- Effect of treatment with testosterone and abiraterone acetate or enzalutamide on Bone Scan with SPECT CT [ Time Frame: 18 months ]Effect of treatment with testosterone and abiraterone acetate or enzalutamide as determined by Change in Tc-99 MDP uptake on quantitative Bone Scan with SPECT CT
- Quality of Life (QoL) as assessed by RANDSF-36 [ Time Frame: Change from baseline to 18 months ]RAND 36-Item Short Form (RANDSF-36) assesses physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, general health perceptions, and perceived change in health with a total score range of 0-100, with a higher score reflecting better QoL.
- Quality of Life (QoL) as assessed by BPI [ Time Frame: Change from baseline to 18 months ]Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning with scales ranging from 0-10, with a higher score indicating a higher level of pain.
- Quality of Life (QoL) as assessed by IIEF [ Time Frame: Change from baseline to 18 months ]International Index of Erectile Function (IIEF-5) is a diagnostic tool for erectile dysfunction, with a total score range of 5-25, with the lowest score indicating a higher degree of dysfunction.
- Quality of Life (QoL) as assessed by PANAS [ Time Frame: Change from baseline to 18 months ]Positive and Negative Affect Schedule (PANAS) is a self-report measure that is made up of two mood scales, one measuring positive affect and the other measuring negative affect, with a total score range from 10-50 with a higher score on the positive scale indicating greater levels of positive affect and a lower score on the negative scale indicating less of a negative affect.
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): NCT02090114
|United States, District of Columbia|
|Sibley Memorial Hospital|
|Washington, District of Columbia, United States, 20016|
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Samuel Denmeade, MD||Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center|