Clinical Trials
Key Themes Across Trials
Resensitization to ARAT (e.g., enzalutamide/abiraterone): Consistently seen post-BAT.
Synergy with DNA-damaging therapies: BAT + PARPi (olaparib) and BAT + chemotherapy (carboplatin, etoposide) show enhanced effects.
Immunotherapy combinations: BAT + nivolumab (COMBAT-CRPC) demonstrated biologic plausibility.
HSPC setting: BATMAN, SPIDERMAN, and case studies suggest BAT may also be useful earlier, not just in CRPC.
SPIDERMAN
Enrollment: ~60 (estimated)
Estimated completion date: 2034
Phase/Design: Phase 2, open-label, non-randomized; parallel assignment with a defined lead-in followed by alternating cycles
Stage/Setting: First-line metastatic hormone-sensitive prostate cancer (mHSPC)—“first line hormonal therapy,” no prior ADT/ARPI for recurrent/metastatic disease. (Note: some registry mirrors label “mCRPC,” but the protocol text and inclusion criteria make clear it is first-line HS.)
Summary:
Objective: Test whether alternating supraphysiologic testosterone (BAT) and darolutamide can delay resistance to hormonal therapy and reduce side effects; includes quality-of-life and molecular correlatives (gene expression, metabolic changes).
Lead-in (months 0–6): Start ADT (LHRH agonist/antagonist) + darolutamide 600 mg BID. Patients with ≥50% PSA decline proceed; non-responders or progressors remain on ADT and come off study.
Alternating phase (post lead-in):
BAT cycle: Testosterone cypionate 400 mg IM every 4 weeks ×3 (12 weeks), without ADT.
Darolutamide cycle: Darolutamide 600 mg BID for 12 weeks, without ADT.
Cycles alternate until clinical/radiographic progression.
Key inclusion highlights: Histologic prostate adenocarcinoma; baseline PSA ≥1.0 ng/mL; rising PSA; evidence of metastatic disease; no prior ADT/ARPI for recurrent/metastatic disease (adjuvant/neoadjuvant allowed if ≥1 year before recurrence). Prior focal RT for oligomets allowed if >6 months, with non-irradiated measurable disease.
Key exclusions (selected): Prior chemotherapy, PSMA-RLT (Pluvicto), or investigational AR-targeted agents; conditions posing testosterone-related risk (e.g., unstable spinal/femoral metastases, obstructive uropathy risk); warfarin use; hematocrit >51%, untreated severe OSA, significant cardiac disease.
Notes: Sponsor/site listed with Johns Hopkins (SKCCC). Registry mirrors indicate Phase 2 and ~60 patients and sometimes (incorrectly) tag “mCRPC.” Denmeade (principal investigator confirmed HSPC)
https://clinicaltrials.gov/study/NCT07142551
STEP-UP
Design: Phase 2, randomized, ~150 men.
Population: Asymptomatic mCRPC.
Treatment:
Arm A: Continuous enzalutamide (Xtandi).
Arm B/C: Sequential BAT + enzalutamide cycling. Testosterone interleaved with enzalutamide (monthly injections; 56-day cycles).
Rationale: BAT may restore ARAT sensitivity. If effective, concept could extend to darolutamide/apalutamide.
Completion: 2026–2027.
Arm B shown.
Arm A receives constant Xtandi
Arm C repeats monthly T injections (56-day cycles) until progression, then 56-day cycles of Xtandi until progression.
https://clinicaltrials.gov/ct2/show/NCT04363164
Sequential High Dose Testosterone and Enzalutamide Compared with Enzalutamide Alone for the Treatment of Asymptomatic Metastatic Castration Resistant Prostate Cancer, STEP-UP Study
https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2021-06077&r=1
BAT trial (Sipuleucel-T Combined With Bipolar Androgen Therapy in Men With mCRPC)
https://clinicaltrials.gov/study/NCT06100705
A Single Arm Open-label, Phase II Study of Sipuleucel-T With Bipolar Androgen Therapy in Men With Metastatic Castration-resistant Prostate Cancer | Clinical Trials | Yale Medicine
https://www.yalemedicine.org/clinical-trials/2000035188-sipuleucel-t-combined-with-bipolar-androgen-therapy-in-men-with-mcrpc
Enrollment: 26
Stage: mCRPC
Summary:
Estimated completion date 12/2027-3/2028
This Phase II study at Yale is testing the combination of BAT with the immunotherapy sipuleucel-T in men with mCRPC. The trial aims to see whether adding cyclic high-dose testosterone to sipuleucel-T can boost the immune response against prostate cancer cells, measured primarily by interferon-gamma ELISPOT responses to the PA2024 antigen used in the vaccine, and secondarily by clinical outcomes such as PSA50 response, objective responses, progression-free survival, and overall survival. Participants receive regular testosterone injections alongside the standard three infusions of sipuleucel-T, with the hypothesis that BAT will potentiate the anti-tumor immune response and improve efficacy compared with historical sipuleucel-T results. The study is open-label and single-arm, with safety and immune activation also being assessed.
APEX
Eflornithine and Testosterone Followed by Enzalutamide for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer, APEX Trial – NCI
https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09882
BAT+DFMO
119 day cycles:
DFMO (eflornithine) 1000 mg PO BID continuously days 1–63
Testosterone cypionate 400 mg IM on days 8 and 36
Enzalutamide 160 mg PO QD continuously on days 64–119
COSMYC Trial (COmbined Suppression of MYC) | ClinicalTrials.gov
https://clinicaltrials.gov/study/NCT06922318
ZEN-3694 48 mg (one 48 mg tablet) will be taken once per day by mouth each cycle (each cycle is 28 days). On the first day of each cycle, testosterone cypionate (400 mg) injection will be administered.
SPECTRA
Supraphysiological Androgen to Enhance Chemotherapy Treatment Activity in Metastatic Castration-Resistant Prostate Cancer, SPECTRA Study – Full Text View – ClinicalTrials.gov
https://classic.clinicaltrials.gov/ct2/show/NCT06039371
Enrollment: 46
Stage: mCRPC
Summary:
Estimated completion date 3/2027-12/2027
One month ADT lead-in with Carboplatin and then BAT and Carboplatin: Compared to Etoposide on days 1-14 of each 28 day cycle + BAT
NCT06305598 (BAT to Restore AR Sensitivity)
Enrollment: Not specified (Phase I, small cohort; single-arm)
Estimated completion date: ~2027 (primary completion est. 2026; 2-year follow-up)
Phase/Design: Phase 1, open-label, non-randomized; single-arm interventional with 3-cycle testosterone induction + ongoing standard LHRH agonist
Stage/Setting: Metastatic castration-resistant prostate cancer (mCRPC) on continuous ADT (leuprolide SC per standard schedule); prior ARSI/chemotherapy allowed if recovered.
Summary:
Objective: Evaluate BAT impact on AR sensitivity (Nelson 10-gene score via spatial transcriptomics), safety/AEs (CTCAE v5), PSA50 response, measurable RECIST response, PFS/OS, QoL (FACIT-F, SF-36 fatigue scales).
Treatment: Testosterone cypionate IM day 1 each 28-day cycle ×3 cycles (in absence of progression/toxicity); continue leuprolide SC standard; imaging (CT/bone scan), optional MRI/biopsy.
First study to use pre/post-BAT paired biopsies with advanced spatial profiling for AR modulation
PSMA-BAT
https://clinicaltrials.gov/ct2/show/NCT04424654
1819P PSMA-BAT: Prospective biomarker trial of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) undergoing bipolar androgen therapy (BAT) – Annals of Oncology
https://www.annalsofoncology.org/article/S0923-7534(23)03604-9/fulltext
Design
Phase II, single-center, exploratory study; actual enrollment 20 men.
Population
Men with metastatic castration-resistant prostate cancer (mCRPC) on continuous ADT.
Treatment
Bipolar androgen therapy (BAT) using cyclical high-dose exogenous testosterone on a castrate backbone.
Key objectives
Assess how PSMA expression changes with BAT exposure
Evaluate the relationship between AR-V7 status and clinical/biologic response to BAT
Results (ESMO 2023 abstract)
Higher baseline PSMA-PET metabolic tumor volume (mTV) and total lesion PSMA (TL-PSMA) were associated with shorter progression-free survival (PFS) in patients treated with BAT.
AR-V7–positive patients had worse overall survival compared with AR-V7–negative patients.
PSMA tumor burden and AR-V7 status may serve as prognostic biomarkers for men receiving BAT.
Status
Completed. Designed primarily as a biomarker and mechanistic study rather than a definitive efficacy trial.
BAT-RAD
https://clinicaltrials.gov/ct2/show/NCT04704505
Enrollment: 47
Stage: CRPC
Summary:
Estimated completion date 2/2026-2/2027
BAT (1) plus Radium-223 (RAD)
DNA DSB should synergize.
HI-TECH
https://clinicaltrials.gov/ct2/show/NCT03522064
Design
Phase II, single-arm trial; target enrollment ~30 men. Focused on metastatic castration-resistant prostate cancer (mCRPC) with DNA damage repair deficiencies (genetic HRD).
Population
mCRPC patients with confirmed homologous recombination deficiency (e.g., BRCA1/2, ATM, CHEK2); castrate testosterone maintained via LHRH therapy or post-orchidectomy.
Treatment
Testosterone enanthate 500 mg IM every 28 days (BAT-like pulse)
Concurrent carboplatin at AUC 5 every cycle
Ongoing ADT maintained (no washout)
Goal: Use supraphysiologic T to stress androgen receptor–driven tumor cells while carboplatin induces double-strand DNA breaks, leveraging HRD vulnerability.
Key biological endpoints
ctDNA dynamics
Tumor gene expression (DDR pathway, AR signaling)
Correlation between BAT-induced stress and platinum sensitivity
Status
Active, estimated completion 2024–2025; no published efficacy results yet.
Primary intent
Mechanistic signal-finding: test synergy of BAT + platinum chemotherapy in HRD+ mCRPC via apoptosis induction, DNA damage amplification, and molecular biomarker analysis.
VA-BAT
https://clinicaltrials.gov/ct2/show/NCT05011383
Design
Phase II, single-arm, biomarker-driven study; target enrollment ~51 men. Focused on metastatic castration-resistant prostate cancer (mCRPC) with specific DNA damage–related mutations: ATM, CDK12, or CHEK2. Goal is to determine whether these mutations predict response or resistance to BAT.
Treatment
Standard BAT regimen using high-dose intramuscular testosterone (400 mg testosterone cypionate every 28 days) administered on a castrate ADT backbone. Cyclic androgen exposure is used to generate supraphysiologic peaks while maintaining castrate troughs.
Core goal
Assess whether men with DDR alterations (ATM, CDK12, CHEK2) display greater sensitivity or unique response patterns to BAT, compared to historical BAT cohorts without such mutations.
Primary endpoint
PSA50 response rate (≥50 percent decline from baseline), stratified by genetic mutation group (ATM vs CDK12 vs CHEK2).
Secondary and exploratory objectives
• Radiographic response and time-to-progression (rPFS)
• Overall survival (OS)
• Quality-of-life metrics
• Biomarker correlations: AR-V7, ctDNA changes, gene-expression shifts under BAT
Status
Recruiting; estimated study completion 2026–2027. No results yet published.
Key takeaways
• Represents the first BAT trial specifically enriched for DDR gene–mutant mCRPC (ATM, CDK12, CHEK2)
• Designed to identify potential genomic predictors of BAT success or failure
• May help define whether BAT has heightened efficacy in DNA-repair–deficient tumors and inform future combination trials (e.g., BAT + PARP inhibitors or platinum)
WOMBAT
Design: Phase 2; 69 men with nmCRPC progressing on darolutamide.
Treatment: 56-day cycles of testosterone enanthate (500 mg IM) + darolutamide (days 29–56).
Endpoints: Time to metastasis, biomarker correlations (ctDNA, AR-V7, methylation).
Completion: 2026–2028.
Endpoints include time to metastasis. A tertiary objective of the study is exploratory biomarker analysis, examining how outcomes may correlate with cell-free DNA alterations, AR-V7 status, and changes in circulating tumor DNA (ctDNA) methylation.
Darolutamide will not be fully cleared from the system. As a result, the androgenic peak will be blunted—dropping from around 2750 ng/dL to an initial level near 1000 ng/dL, with a peak of approximately 1450 ng/dL by day 7. Individual responses will vary, and bloodwork will confirm that high serum testosterone levels are reached. These will not be androgenic levels.
https://clinicaltrials.gov/study/NCT06594926
Bipolar androgen therapy (BAT) for nonmetastatic castration-resistant prostate (nmCRPC) cancer progressing on darolutamide: Working Out M0 BAT (WOMBAT; ANZUP 2201)
https://ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.TPS298
ASCO GU 2025: Bipolar Androgen Therapy (BAT) for Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) Progressing on Darolutamide: Working out M0 BAT (WOMBAT; ANZUP 2201)
https://www.urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158183-asco-gu-2025-bipolar-androgen-therapy-bat-for-nonmetastatic-castration-resistant-prostate-nmcrpc-cancer-progressing-on-darolutamide-working-out-m0-bat-wombat-anzup-2201.html
ACROBAT
Study Details | NCT05081193 | Safety and Efficacy of Oral Testosterone Undecanoate Followed by Enzalutamide as Therapy for Men With Metastatic Castrate Resistant Prostate Cancer | ClinicalTrials.gov
https://www.clinicaltrials.gov/study/NCT05081193
Phase 1: Oral Testosterone Undecanoate Cycling
Drug: Oral testosterone undecanoate (TU)
Dose: Administered twice daily
Schedule (28-day cycle):
Days 1–7: TU twice daily
Days 8–14: No TU
Days 15–21: TU twice daily
Days 22–28: No TU
ADT: Continued throughout to maintain castrate troughs between pulses
Cycle repetition: Continued until radiographic disease progression or unacceptable toxicity
This design produces repeated androgen pulses with intervening castrate intervals, but is not intended to guarantee classic supraphysiologic testosterone peaks seen with intramuscular BAT.
Phase 2: Enzalutamide Sequencing at Progression
Trigger: Radiographic progression on oral TU cycling
Drug: Enzalutamide
Dose: 160 mg orally once daily
Schedule: Days 1–28 of each 28-day cycle
ADT: Continued
Duration: Continued per protocol (up to protocol-specified number of cycles or until progression/toxicity)
This is a defined sequence, not overlap or combination therapy.
DaroBAT
Enrollment: Not posted in CTIS mirrors
Estimated completion date: December 2027
Phase/Design: Phase 2, randomized, parallel-group; ADT maintained throughout. Experimental arm receives darolutamide plus bipolar androgen therapy; control arm receives standard care while continuing ADT.
Stage/Setting: Metastatic castration-resistant prostate cancer (mCRPC) after progression on an ARPI while castrate.
Summary:
• Objective: Determine whether adding bipolar androgen therapy (BAT) to darolutamide, with ongoing ADT, improves progression-free outcomes and quality of life versus standard care with ADT alone. Includes patient-reported outcomes and imaging-based assessments.
• Experimental regimen: Darolutamide per label plus BAT using transdermal testosterone gel (Testogel 16.2 mg/g), administered in cycles while ADT is continued. EUCTR Network
• Control regimen: Standard-of-care management for mCRPC with continued ADT; no BAT.
• Key inclusion highlights: Histologic prostate adenocarcinoma; metastatic disease documented on CT/MRI, bone scan, or PSMA-PET; mCRPC with progression on apalutamide, darolutamide, or enzalutamide; castrate testosterone; PSA ≥1.0 ng/mL; ECOG 0–2.
• Key exclusions (selected): Prior chemotherapy or PSMA-RLT; use of warfarin; conditions posing testosterone-related risk such as unstable spinal/femoral metastases or obstructive uropathy risk; severe OSA untreated; significant cardiac disease; hematocrit >51%; allergy to sesame or cottonseed oil.
Notes: EU CT number 2025-521051-23-00. Sponsor: Universität Münster; internal protocol code UniMS22_0022. Public university page lists project leadership at Münster and confirms the EUCT number and mCRPC focus.
https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-521051-23-00
https://clinicaltrials.eu/trial/study-of-darolutamide-and-testosterone-for-patients-with-advanced-prostate-cancer-resistant-to-standard-hormone-therapy/
Notes: An 81 mg dose of transdermal testosterone gel is far below what is required to achieve SPA levels.
If the diagram is accurate, a subset of men in this cycling scheme will, in practice, remain on continuous enzalutamide. In that group, most canonical intracellular androgen receptor signaling will remain blocked. Any therapeutic effect observed there would therefore be attributable primarily to the ADT backbone and/or to non-canonical pathways, such as activation of membrane-associated androgen receptors. That distinction would be highly informative biologically.
Others will be on abiraterone, which markedly suppresses intratumoral and systemic DHT synthesis as well as 5AR . Exogenous testosterone will persist largely as testosterone, rather than being converted in substantial fraction to DHT.
Complete BATTLE or Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer
Trial: https://clinicaltrials.gov/ct2/show/NCT03734653
Transdermal square-wave testosterone therapy: A pilot trial in metastatic castration-resistant prostate cancer. | Journal of Clinical Oncology
https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.6_suppl.188
Enrollment: 15
Stage: mCRPC
Summary:
Complete
Transdermal testosterone gel was administered at a dose of 100 mg/day for a minimum of 12 weeks and until disease progression. Therapy was then switched to Xtandi 160 mg/day until the next disease progression.
Transdermal gel dose not sufficient for SPT (avg measurement 901 ng/dl)
PSA50 13.3% during testosterone and 66.7% after switching to enzalutamide.
Complete: ExBAT
Design: Phase 2; 51 men with mCRPC.
Treatment:
Day 1: Testosterone 400 mg IM.
Days 29–56: Darolutamide 600 mg BID.
Day 57–63: Washout.
Completion: 2024–2025.
Interim Results: ExBAT study demonstrated durable (12 months or more) antitumor activity of alternating BAT and darolutamide in around 40% of pts.
Extreme bipolar androgen therapy: Alternating darolutamide and testosterone cypionate in patients with metastatic castration-resistant prostate cancer (mCRPC; ExBAT trial/LACOG 0620). | Journal of Clinical Oncology
https://ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.178
Extreme Bipolar Androgen Therapy With Darolutamide and Testosterone Cypionate in Patients With Metastatic Castration-Resistant Prostate Cancer (ExBAT Trial) – Full Text View – ClinicalTrials.gov
https://classic.clinicaltrials.gov/ct2/show/NCT04558866
Complete: Olaparib + BAT
Design: Phase 2; 36 men with mCRPC.
Status: Complete.
Treatment: Testosterone (400 mg IM q28d) + olaparib 300 mg BID.
Results:
PSA50: 47% in HRR+ and 47% in HRR–.
Radiographic response: 61.5%.
PSA90: 26%.
Significance: Strong synergy of PARPi with BAT regardless of HRR mutation status.
Trial and results: https://clinicaltrials.gov/ct2/show/NCT03516812
Summary: ESMO 2021: Bipolar Androgen Therapy (BAT) Plus Olaparib in Men With Metastatic Castration-Resistant Prostate Cancer
https://www.urotoday.com/conference-highlights/esmo-2021/esmo-2021-prostate-cancer/132121-esmo-2021-bipolar-androgen-therapy-bat-plus-olaparib-in-men-with-metastatic-castration-resistant-pro
Details: Clinical Study Protocol (CSP)
https://cdn.clinicaltrials.gov/large-docs/12/NCT03516812/Prot_SAP_000.pdf
Complete: 2006 AACR study
The study tested the rapid cycling of an oral form of testosterone (oral testosterone undecanoate) in men whose cancer had progressed to the CRPC state.
Rapid Androgen Cycling as Treatment for Patients with Prostate Cancer | Clinical Cancer Research | American Association for Cancer Research
https://aacrjournals.org/clincancerres/article/12/24/7414/193013/Rapid-Androgen-Cycling-as-Treatment-for-Patients
Patients entered repeating 28-day cycles, structured as follows:
Days 1–7
Testosterone supplementation (short-duration androgen exposure)
Intended to create an acute androgen spike relative to castrate baseline
Days 8–21
Two treatment arms:
Estrogen patch arm
Transdermal estrogen administered days 8–21
Intended to suppress luteinizing hormone (LH) and maintain low endogenous testosterone while adding a different hormonal stressor
No-estrogen arm
No hormonal supplementation after day 7
Testosterone levels allowed to fall back toward castrate range
Days 22–28
Washout / recovery period before the next cycle
Cycles were repeated in the absence of progression or unacceptable toxicity.
The testosterone levels achieved were not true SPA.
Complete: Etoposide BAT
A Pilot Study of IM Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer – Full Text View – ClinicalTrials.gov
https://clinicaltrials.gov/ct2/show/NCT01084759
Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study – PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507510/
Enrollment: 16 actual
Stage: mCRPC
Summary:
Complete
Etoposide + BAT (1)
Complete: Men’s Cycle
Trial and results: https://clinicaltrials.gov/ct2/show/NCT00586898
Enrollment: 36 actual
Stage: mCRPC
Howard Scher, MD, Memorial Sloan Kettering Cancer Center Scherh@mskcc.org
Summary:
Complete
76% Complete response rate
14% Partial response rate (PSA50)
10% Stable disease
BAT with Androgel, E2 patches, ketoconazole, bicalutamide, Lupron (1)
Complete: Trial
Phase 1 Trial of High-Dose Exogenous Testosterone in Patients with Castration-Resistant Metastatic Prostate Cancer – PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738932/
Enrollment
19 actual
Stage mCRPC
Summary
Complete
Androgel and bicalutamide
8-week cycles or 1 week single cycle.
Max tT was less then 900 mg/dl. fT was calculated.
Complete: COMBAT-CRPC
Design: Phase 2; 44 men with mCRPC.
Status: Complete.
Treatment: BAT + nivolumab (starting cycle 4).
Findings: Encouraging synergy with checkpoint inhibitor; durable responses in biomarker-selected subsets.
https://clinicaltrials.gov/ct2/show/NCT03554317
COMBAT-CRPC: Concurrent administration of bipolar androgen therapy (BAT) and nivolumab in men with metastatic castration-resistant prostate cancer (mCRPC). | Journal of Clinical Oncology
https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.5014
ASCO 2022: Overall Survival and Biomarker Results From Combat: A Phase 2 Study of Bipolar Androgen Therapy Plus Nivolumab for Patients With Metastatic Castrate-Resistant Prostate Cancer
https://www.urotoday.com/conference-highlights/asco-2022/asco-2022-prostate-cancer/137706-asco-2022-overall-survival-and-biomarker-results-from-combat-a-phase-2-study-of-bipolar-androgen-therapy-plus-nivolumab-for-patients-with-metastatic-castrate-resistant-prostate-cancer.html
Complete: BATMAN
Design: Phase 2; 33 men, HSPC.
Status: Complete.
Treatment: 6-mo ADT lead-in → alternating 3-mo ADT and BAT cycles.
Results:
80% objective response.
Median ADT PFS: 47.8 mo.
Post-BAT ARAT rechallenge: PSA50 94.4%, PSA90 66.7%.
Long OS in responders (not reached after 6 years); non-responders ~43 mo.
PSA provocation by bipolar androgen therapy may predict duration of response to first-line androgen deprivation: Updated results from the BATMAN study – PMC
https://pmc.ncbi.nlm.nih.gov/articles/PMC9633380/
Outcome Measure
Result (2016 Publication)
Result (2022 Update)
PSA <4 ng/ml at 18 months
59%
–
Objective Response Rate (RECIST)
80%
–
PFS on ADT (median)
–
47.8 months
OS (Responders, PSA <4 ng/ml post-BAT/ADT)
–
Not Reached
OS (Non-Responders, PSA ≥4 ng/ml post-BAT/ADT)
–
43 months
PSA50 to Abi/Enz post-BAT
–
94.40%
PSA90 to Abi/Enz post-BAT
–
66.70%
PFS on Abi/Enz post-BAT (median)
–
20.6 months
PFS (PSA peak ≥9 ng/ml post-BAT)
–
20.6 months
PFS (PSA peak <9 ng/ml post-BAT)
–
Not Reached
OS (PSA peak ≥9 ng/ml post-BAT)
–
79.6 months
OS (PSA peak <9 ng/ml post-BAT)
–
Not Reached
What happened in BATMAN
BAT was stopped per protocol
In BATMAN, patients received BAT in a hormone-sensitive setting, then returned to standard ADT.
BAT discontinuation was planned, not a failure event by itself.
Post-BAT outcomes were mixed
Some men showed PSA progression after returning to ADT.
Others maintained disease control for prolonged periods.
Time to progression varied widely across patients.
Key point: preserved hormone sensitivity
Many men who progressed after BAT subsequently had robust responses to abiraterone or enzalutamide, with high PSA50 and PSA90 rates and long progression-free survival.
That pattern is inconsistent with established CRPC and strongly supports preserved androgen dependence.
No formal CRPC adjudication
BATMAN did not demonstrate or claim that men became CRPC during or immediately after BAT.
CRPC was not formally diagnosed unless progression occurred with confirmed castrate testosterone, which was not the case during BAT and was not the primary endpoint after BAT.
Complete: RESTORE
Design: Open-label Phase 2; 112 men with CRPC.
Status: Complete.
Treatment: Post-ARPI progression, men received BAT; rechallenge with ARAT afterward.
Findings:
Post-BAT Xtandi rechallenge: 68% PSA50 response.
Suggests sequence matters: better results post-enzalutamide than post-abiraterone.
Trial and results: https://clinicaltrials.gov/ct2/show/NCT02090114
Summary: 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
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775877/pdf/nihms-1633109.pdf
Commentary: 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 – PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775877/
Complete: Docetaxel BAT
https://clinicaltrials.gov/study/NCT00587431
The men’s cycle plus docetaxel (Doc) in prostate cancer patients with rising PSAs in the non-castrate state | Journal of Clinical Oncology
https://ascopubs.org/doi/abs/10.1200/jco.2005.23.16_suppl.4564
A Phase II Trial of Docetaxel with Rapid Androgen Cycling as a Treatment for Patients with Prostate Cancer – PMC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051836/
Design
Single-arm, Phase II, two sequential cohorts (n≈100). Progressive non-castrate prostate cancer with rising PSA; ≤6 months prior hormone therapy allowed. Pre-mCRPC, representing an early chemohormonal cycling concept.
Treatment
Both cohorts received docetaxel with continuous leuprolide plus short pulses of topical testosterone.
Cohort 1 (n=62): Docetaxel 75 mg/m² q28d ×6 cycles; 7-day testosterone pulse per 28-day cycle.
Cohort 2 (n=38): Docetaxel 70 mg/m² q21d ×9 cycles; 3-day testosterone pulse per 21-day cycle.
Core goal: induce repeated high–low androgen oscillations to trigger apoptosis and test feasibility/safety before modern BAT.
Primary endpoint
At 18 months:
Non-castrate testosterone (>150 ng/dL), and
Undetectable PSA (stringently defined by prior local therapy status).
Results
Cohort 1: 0 % met the composite endpoint
Cohort 2: 13 % achieved it (tighter cycling modestly improved responses)
Safety and pharmacology
Febrile neutropenia: ~16 % overall (higher than typical docetaxel in mCRPC)
Docetaxel clearance ~50 % lower vs castrate patients, indicating altered pharmacokinetics in non-castrate settings
No significant intra-patient PK changes across cycles
Key takeaways
Demonstrated feasibility and biologic effect of chemohormonal cycling
Outcomes modest but informative for designing later true BAT regimens
Trial served as an early “screening model” rather than a definitive practice-changing study.
Complete: TRANSFORMER
Enrollment: 222 men with mCRPC.
Stage: mCRPC
Status: Complete.
Comparion: BAT vs enzalutamide.
Protocol
Findings:
PSA50 response: 28.2% (BAT).
Post-BAT enzalutamide: 77.8% PSA50.
Median PFS: ~5.7 months (both arms).
OS: 32.9 mo. (BAT) vs 29.0 mo. (enzalutamide).
Impact: Demonstrated strong re-sensitization to ARAT post-BAT.
Commentary:
TRANSFORMER: A Randomized Phase II Study Comparing BAT Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer – PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274807/
Trial and results: https://clinicaltrials.gov/ct2/show/NCT02286921
BAT overview, clinical trials, and research