Prostate CancerPhase 2RestoreNCT02090114
RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistance (The RESTORE Study)
A Phase 2 study testing Testosterone cypionate, Testosterone Enanthate and Abiraterone acetate in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide, abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Testosterone cypionate, Testosterone Enanthate and Abiraterone acetate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 Aug 2014to 11 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Performance status ≤2
- Age ≥18 years
- Histologically-confirmed adenocarcinoma of the prostate
- Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist).
- Documented castrate level of serum testosterone (<50 ng/dl).
- For Cohorts A and B, patients must have progressed on prior treatment with enzalutamide or abiraterone acetate + prednisone (by PSA criteria or radiographically).
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- For castration-only Cohort C, patients must have developed castrate resistant prostate cancer after progressing on first line hormone therapy with either surgical castration or LHRH agonist or LHRH agonist plus an anti-androgen.
- For Cohort D patients must have inactivating somatic or germline mutations in ≥2 of the genes TP53, PTEN, RB1
- Patients progressing on LHRH agonist plus an anti-androgen as first line therapy must be off anti-androgen for 4 weeks prior to first treatment with testosterone.
- Patients with rising PSA on two successive measurements at least two weeks apart.
- For Cohort A (enzalutamide) and Cohort B (abiraterone acetate):
- Prior treatment with up to 2 additional second line hormone therapies, including ketoconazole is allowed.
- Patients who have progressed on both enzalutamide and abiraterone acetate are eligible and post-BAT will be retreated with the last second line agent they had received (e.g. patient receiving abiraterone then enzalutamide would receive retreatment with enzalutamide post-BAT).
- Patients must be withdrawn from enzalutamide or abiraterone acetate for ≥ 4 weeks and have documented PSA increase after the withdrawal period.
- Patients receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone prior to starting BAT.
- For Cohort C (castration-only):
- Patients must continue on castrating therapy throughout BAT treatment.
- No prior second line hormone treatment with flutamide, bicalutamide, nilutamide, enzalutamide, abiraterone, ketoconazole, ARN-509 or other investigational androgen ablative therapies is permitted for Cohort C.
- For Cohort D (mutation cohort):
- Patients must continue on castrating therapy throughout BAT treatment.
- Treatment with first-generation hormonal therapy (i.e. flutamide, bicalutamide, nilutamide), is allowed
- Patient must have received at least one and not more than two second generation hormone therapies (i.e. enzalutamide, abiraterone, apalutamide).
- For Cohorts A-D, prior docetaxel for hormone-sensitive prostate cancer is permitted if ≤ 6 doses were given in conjunction with first-line androgen deprivation therapy and >12 months since last dose of docetaxel
- For Cohort D, one line of prior chemotherapy with docetaxel or cabazitaxel for metastatic castrate resistant prostate cancer is allowed
- Acceptable liver function:
- Bilirubin < 2.5 times institutional upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) < 2.5 times ULN
- Acceptable renal function:
- -- Serum creatinine < 2.5 times ULN, OR
- Acceptable hematologic status:
- Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
- Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
- Hemoglobin ≥ 9 g/dL.
- At least 4 weeks since prior surgery with full recovery (no persistent toxicity ≥ Grade 1).
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Pain due to metastatic prostate cancer requiring opioid analgesics.
- >5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤1 cm in diameter are permitted).
- Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.
- Prior treatment with one line of chemotherapy for metastatic castration-resistant prostate cancer is allowed for Cohort D
- Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia
- 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, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction).
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- 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 AIDS or hepatitis B or C.
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
- Prior history of a thromboembolic event within the last two years and not currently on systemic anticoagulation.
- Hematocrit >50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (67)].
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
About this study
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
Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide, abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy. The study will enroll four cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A; n=30); men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B; n=30); men with metastatic CRPC who have progressed on first line castration-only therapy (Cohort C; n=30); men with metastatic CRPC with inactivating somatic or germline mutations in ≥2 of the genes TP53, PTEN, or RB1 (Cohort D; n=20).
Read the detailed description
The trial will enroll up to 110 patients, 30 for each Cohorts A-C and 20 for Cohort D. Eligible patients will continue on androgen ablative therapy with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) if not surgically castrated to suppress endogenous testosterone production. Patients will also receive intramuscular injection with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dosing scheme was designed to produce rapidly fluctuating serum testosterone levels from the supraphysiologic to the near-castrate range (i.e. Bipolar Androgen Therapy [BAT]). Assessments for response to testosterone will be made approximately every 3 months. Upon displaying evidence of progression, patients will then go on to receive either abiraterone (Cohort B) or enzalutamide (Cohort A), whichever agent they had previously progressed on prior to study enrollment. Patients in Cohort C will remain on LHRH agonist therapy and receive no additional androgen ablative hormonal therapy while those in the mutation-positive Cohort D will receive enzalutamide regardless of prior therapy.
- Conditions
- Prostate Cancer
- Being tested
- Testosterone cypionate, Testosterone Enanthate, Abiraterone acetate, Enzalutamide
- Keywords
- Bipolar Androgen Therapy, Testosterone, Enzalutamide, Abiraterone, Androgen Ablative Therapies
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone cypionateDrug
Also called DEPO-Testosterone Injection
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 and will be administered at 400mg IM every 28 days.
Testosterone EnanthateDrug
Also called Delatestryl
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. Will be administered at 400mg IM every 28 days.
Abiraterone acetateDrug
Also called Zytiga
Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate.
EnzalutamideDrug
Also called Xtandi
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A:Post-enzalutamide | Experimental | Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. 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 enzalutamide 160 mg by mouth daily. Receives: Drug: Testosterone cypionate; Drug: Testosterone Enanthate; Drug: Enzalutamide |
| Cohort B: Post-abiraterone | Experimental | Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. 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 abiraterone 1000 mg by mouth daily. Receives: Drug: Testosterone cypionate; Drug: Testosterone Enanthate; Drug: Abiraterone acetate |
| Cohort C: Castration Only | Experimental | Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. Receives: Drug: Testosterone cypionate; Drug: Testosterone Enanthate |
| Cohort D: Mutation | Experimental | Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). Receives: Drug: Testosterone cypionate; Drug: Testosterone Enanthate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy (BAT)
Number of participants with ≥50% PSA reduction from pre-BAT baseline level
Measured: up to 18 months
PSA Response to Enzalutamide or Abiraterone Acetate Post Bipolar Androgen Therapy
Number of participants with ≥50% PSA reduction after enzalutamide or abiraterone acetate post-BAT from baseline
Measured: up to 24 months
Secondary outcomes (10)
PSA Progression on Enzalutamide or Abiraterone Acetate or Castrate Levels Post-BAT
Time to PSA progression on enzalutamide or abiraterone acetate or return to castrate levels of testosterone post-BAT, defined as the time from the date of re-initiation of enzalutamide or abiraterone acetate or castration-only therapy to the date of the PSA measurement when it shows an increase by ≥25% above the nadir value that occurred following re-initiation of enzalutamide or abiraterone acetate or castration-only therapy and confirmed by a repeat PSA 4 weeks later (PCWG2).
Measured: up to 18 months
PSA Progression on BAT (Bipolar Androgen Therapy )
Time to PSA progression on BAT. Time to PSA progression on BAT is defined as the time from the date of initial dose of Testosterone to the date of the PSA measurement when it shows an ≥25% increase above the nadir value and confirmed by a repeat PSA 4 weeks later (PCWG2 criteria) during the treatment with BAT.
Measured: up to 18 months
Disease Response as Defined by RECIST 1.1 (Soft Tissue Lesions) and PCWG2 Criteria (Bone Lesions)
Number of participants with complete or partial response post-BAT as defined by RECIST 1.1 (for soft tissue lesions) and PCWG2 criteria (for bone disease), or return to castration-only post-BAT.
Measured: up to 18 months
Initiation of Docetaxel Chemotherapy
Time to initiation of docetaxel chemotherapy
Measured: up to 18 months
Quality of Life (QoL) as Assessed by FACIT-F Score
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.
Measured: up to 18 months
Safety and Tolerability as Assessed by Number of Participants With Adverse Events
Number of participants who experience adverse events, as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Measured: 18 months
Quality of Life (QoL) as Assessed by RANDSF-36
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. 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 a higher score reflecting a better QoL.
Measured: up to 18 months
Quality of Life (QoL) as Assessed by BPI
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.
Measured: up to 18 months
Quality of Life (QoL) as Assessed by IIEF
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.
Measured: up to 18 months
Quality of Life (QoL) as Assessed by PANAS
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.
Measured: up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study start25 Aug 2014
- Primary completion11 Nov 2021
- Study completion11 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Samuel Denmeade, MD, Principal investigator, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02090114
- Sponsor's protocol ID
- J1416
- Other IDs
- NA_00093344, 1R01CA184012-01
- Acronym
- Restore
- Status last verified
- Jun 2022
- First submitted
- 4 Mar 2014
- Last updated
- 27 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Markowski MC, Wang H, Sullivan R, Rifkind I, Sinibaldi V, Schweizer MT, Teply BA, Ngomba N, Fu W, Carducci MA, Paller CJ, Marshall CH, Eisenberger MA, Luo J, Antonarakis ES, Denmeade SR. A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts. Eur Urol. 2021 May;79(5):692-699. doi: 10.1016/j.eururo.2020.06.042. Epub 2020 Jul 2.
PubMed 32624280Sena LA, Wang H, Lim ScM SJ, Rifkind I, Ngomba N, Isaacs JT, Luo J, Pratz C, Sinibaldi V, Carducci MA, Paller CJ, Eisenberger MA, Markowski MC, Antonarakis ES, Denmeade SR. Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy. Eur J Cancer. 2021 Feb;144:302-309. doi: 10.1016/j.ejca.2020.11.043. Epub 2020 Dec 29.
PubMed 33383350Teply BA, Wang H, Luber B, Sullivan R, Rifkind I, Bruns A, Spitz A, DeCarli M, Sinibaldi V, Pratz CF, Lu C, Silberstein JL, Luo J, Schweizer MT, Drake CG, Carducci MA, Paller CJ, Antonarakis ES, Eisenberger MA, Denmeade SR. Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study. Lancet Oncol. 2018 Jan;19(1):76-86. doi: 10.1016/S1470-2045(17)30906-3. Epub 2017 Dec 14.
PubMed 29248236
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02090114
- Acronym / sponsor ID
- Restore / J1416
- Conditions
- Prostate Cancer
- Keywords
- Bipolar Androgen Therapy, Testosterone, Enzalutamide, Abiraterone, Androgen Ablative Therapies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Aug 2014 (actual)
- Primary completion
- 11 Nov 2021 (actual)
- Study completion
- 11 Nov 2021 (actual)
- First posted
- 18 Mar 2014 (estimated)
- Results
- Posted 27 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide, abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy. The study will enroll four cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A; n=30); men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B; n=30); men with metastatic CRPC who have progressed on first line castration-only therapy (Cohort C; n=30); men with metastatic CRPC with inactivating somatic or germline mutations in ≥2 of the genes TP53, PTEN, or RB1 (Cohort D; n=20).
Detailed description
The trial will enroll up to 110 patients, 30 for each Cohorts A-C and 20 for Cohort D. Eligible patients will continue on androgen ablative therapy with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) if not surgically castrated to suppress endogenous testosterone production. Patients will also receive intramuscular injection with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dosing scheme was designed to produce rapidly fluctuating serum testosterone levels from the supraphysiologic to the near-castrate range (i.e. Bipolar Androgen Therapy [BAT]). Assessments for response to testosterone will be made approximately every 3 months. Upon displaying evidence of progression, patients will then go on to receive either abiraterone (Cohort B) or enzalutamide (Cohort A), whichever agent they had previously progressed on prior to study enrollment. Patients in Cohort C will remain on LHRH agonist therapy and receive no additional androgen ablative hormonal therapy while those in the mutation-positive Cohort D will receive enzalutamide regardless of prior therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A:Post-enzalutamide | Experimental | Drug: Testosterone cypionate, Drug: Testosterone Enanthate, Drug: EnzalutamideMen with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. 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 enzalutamide 160 mg by mouth daily. |
| Cohort B: Post-abiraterone | Experimental | Drug: Testosterone cypionate, Drug: Testosterone Enanthate, Drug: Abiraterone acetateMen with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. 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 abiraterone 1000 mg by mouth daily. |
| Cohort C: Castration Only | Experimental | Drug: Testosterone cypionate, Drug: Testosterone EnanthateMen with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. |
| Cohort D: Mutation | Experimental | Drug: Testosterone cypionate, Drug: Testosterone EnanthateMen with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Performance status ≤2
- Age ≥18 years
- Histologically-confirmed adenocarcinoma of the prostate
- Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist).
- Documented castrate level of serum testosterone (<50 ng/dl).
Key exclusion criteria (11 listed)
- Pain due to metastatic prostate cancer requiring opioid analgesics.
- >5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤1 cm in diameter are permitted).
- Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.
- Prior treatment with one line of chemotherapy for metastatic castration-resistant prostate cancer is allowed for Cohort D
- Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Testosterone cypionateAlso: DEPO-Testosterone InjectionDEPO-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 and will be administered at 400mg IM every 28 days. | Drug | Cohort A:Post-enzalutamide, Cohort B: Post-abiraterone, Cohort C: Castration Only, Cohort D: Mutation |
| Testosterone EnanthateAlso: DelatestrylTestosterone 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. Will be administered at 400mg IM every 28 days. | Drug | Cohort A:Post-enzalutamide, Cohort B: Post-abiraterone, Cohort C: Castration Only, Cohort D: Mutation |
| Abiraterone acetateAlso: ZytigaAbiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. | Drug | Cohort B: Post-abiraterone |
| EnzalutamideAlso: XtandiXTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. | Drug | Cohort A:Post-enzalutamide |
Primary outcome
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
10 secondary outcomes
PSA Progression on Enzalutamide or Abiraterone Acetate or Castrate Levels Post-BAT
Time frame: up to 18 months
PSA Progression on BAT (Bipolar Androgen Therapy )
Time frame: up to 18 months
Disease Response as Defined by RECIST 1.1 (Soft Tissue Lesions) and PCWG2 Criteria (Bone Lesions)
Time frame: up to 18 months
Initiation of Docetaxel Chemotherapy
Time frame: up to 18 months
Quality of Life (QoL) as Assessed by FACIT-F Score
Time frame: up to 18 months
Safety and Tolerability as Assessed by Number of Participants With Adverse Events
Time frame: 18 months
Quality of Life (QoL) as Assessed by RANDSF-36
Time frame: up to 18 months
Quality of Life (QoL) as Assessed by BPI
Time frame: up to 18 months
Quality of Life (QoL) as Assessed by IIEF
Time frame: up to 18 months
Quality of Life (QoL) as Assessed by PANAS
Time frame: up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32624280Markowski MC, Wang H, Sullivan R, Rifkind I, Sinibaldi V, Schweizer MT, Teply BA, Ngomba N, Fu W, Carducci MA, Paller CJ, Marshall CH, Eisenberger MA, Luo J, Antonarakis ES, Denmeade SR. A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts. Eur Urol. 2021 May;79(5):692-699. doi: 10.1016/j.eururo.2020.06.042. Epub 2020 Jul 2.
- Results publication: PubMed 33383350Sena LA, Wang H, Lim ScM SJ, Rifkind I, Ngomba N, Isaacs JT, Luo J, Pratz C, Sinibaldi V, Carducci MA, Paller CJ, Eisenberger MA, Markowski MC, Antonarakis ES, Denmeade SR. Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy. Eur J Cancer. 2021 Feb;144:302-309. doi: 10.1016/j.ejca.2020.11.043. Epub 2020 Dec 29.
- Results publication: PubMed 29248236Teply BA, Wang H, Luber B, Sullivan R, Rifkind I, Bruns A, Spitz A, DeCarli M, Sinibaldi V, Pratz CF, Lu C, Silberstein JL, Luo J, Schweizer MT, Drake CG, Carducci MA, Paller CJ, Antonarakis ES, Eisenberger MA, Denmeade SR. Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study. Lancet Oncol. 2018 Jan;19(1):76-86. doi: 10.1016/S1470-2045(17)30906-3. Epub 2017 Dec 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Denmeade, MD principal investigator
Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Testosterone cypionate, Testosterone Enanthate and Abiraterone acetate in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy (BAT) (time frame: up to 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02090114, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2022.