Extreme Bipolar Androgen Therapy With Darolutamide and Testosterone Cypionate in Patients With Metastatic Castration-Resistant Prostate Cancer (ExBAT Trial)

NCT04558866 | Active Not Recruiting Phase 2

• 1 other identifier: LACOG 0620
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, open-label, phase II, single-arm trial evaluating combination of darolutamide and high testosterone doses - extreme bipolar androgen therapy (ExBAT) - in patients with metastatic castration-resistant prostate cancer (mCRPC).

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Radiographic Progression-Free Survival (rPFS)

  Defined as (at least one of the 3 criteria below): * Bone progression according to the Prostate Cancer Working Group 3 (PCWG3): * The first bone scan with ≥2 new lesions compared to baseline is observed \<12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); * The first bone scan with ≥2 new lesions compared to baseline is observed ≥12 weeks from randomization and the new lesions are verified on the next bone scan ≥6 weeks later (a total of ≥2 new lesions compared to baseline). * Progression of soft tissue lesions measured by CT or MRI as defined in modified RECIST criteria. * •Death from any cause. The first bone scan with ≥2 new lesions compared to baseline is observed ≥12 weeks from randomization and the new lesions are verified on the next bone scan ≥6 weeks later (a total of ≥2 new lesions compared to baseline).

  12 months

Secondary Outcomes (8)

• PSA decline ≥ 50% rate from baseline (PSA50)

  54 weeks

• Time to disease progression

  54 weeks

• Radiographic progression-free survival (rPFS)

  54 weeks

• Overall survival (OS)

  54 weeks

• Quality of life (QoL) - EQ-5D-3L

  54 weeks

Study Arms (1)

ExBAT Arm

EXPERIMENTAL

Testosterone Cypionate 400 mg IM on Day 1 and Darolutamide 1,200mg/day (two 300 tablets every 12 hours) p.o. for 28 days, from day 29 to day 56 followed by a washout period of 7 days (63-day cycles), until loss of benefit (disease progression and/or limiting toxicity).

Drug: Testosterone Cypionate; Drug: Darolutamide

Interventions

Testosterone Cypionate DRUG

One administration every 63 cycles until progression or unacceptable toxicity or completion of treatment phase (54 weeks; 6 cycles), whichever comes first.

Also known as: Deposteron

ExBAT Arm

Darolutamide DRUG

During 4 weeks, from day 29 to day 56 of each 63-day cycle (+- 3 days) until progression or unacceptable toxicity or completion of treatment phase (54 weeks; 6 cycles), whichever comes first.

Also known as: Nubeqa

ExBAT Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
• Male aged 18 years and above.
• Histologic confirmation of adenocarcinoma of the prostate.
• Evidence of M1 metastatic disease (as defined by AJCC criteria) on previous bone, CT, and/or MRI scan.
• Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (ie, surgical or medical castration) confirmed by testosterone level below 50 ng/dL at the screening visit. Castrate levels of testosterone must be maintained by surgical or medical means (luteinizing hormone-releasing hormone \[LHRH\]/ GnRH analogues) throughout the conduct of the study.
• Documented prostate cancer progression as per PCWG3 criteria1-3 with at least one of the following:
• PSA progression: defined by a minimum of 2 rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the screening visit should be ≥ 2 ng/mL.\* Participants who received an anti-androgen must have progression after withdrawal (4 weeks since last flutamide, bicalutamide or nilutamide administration)
• Radiographic disease progression in soft tissue based on RECIST 1.1 criteria. Participants whose disease spread is limited to regional pelvic lymph nodes will be considered eligible.
• Radiographic disease progression in bone defined as appearance of 2 or more new bone lesions on bone scan.
• ECOG performance status 0-1.
• Participants who are chemotherapy-naive for mCRPC who have received prior treatment with abiraterone acetate for advanced prostate cancer (M1 castration-sensitive or M1 castration-resistant settings). Abiraterone should be stopped at least 14 days prior to study treatment initiation.
• Participants already receiving agents for the management of skeletal-related events (SREs) are allowed to continue with anti-bone resorptive therapy (including, but not limited to bisphosponate or receptor activator of nuclear factor kappa ligand inhibitor) if on stable dose for more than 28 days prior to treatment arm assignment.
• Prior prostate cancer vaccine therapy, radiation therapy, radium-223, anti-androgens (eg, flutamide), ketoconazole, and diethylstilbestrol (DES) or other estrogens, are allowed up to 28 days prior to study arm assignment.
• Asymptomatic or minimally symptomatic mCRPC according to Brief Pain Inventory - Short Form (BPI-SF) performed during screening: asymptomatic is defined as BPI-SF item #3 score of 0 to 1; minimally symptomatic is defined as BPI-SF item #3 score of 2 to 4.
• Patients must agree to refrain from donating sperm during the course of this study and for at least 1 week after completion of study therapy.

You may not qualify if:

• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.
• Participants with active brain metastases. Participants with brain metastases are eligible to enroll in this study if brain metastases have been treated and there is no magnetic resonance imaging (MRI except where contraindicated in which CT scan is acceptable) evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration.
• Participants must have recovered from the effects of major surgery requiring general anesthesia or significant traumatic injury at least 14 days before treatment arm assignment.
• Prior chemotherapy for mCRPC. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥ 12 months elapsed from last dose of docetaxel.
• Prior treatment with enzalutamide, apalutamide, darolutamide or any 2nd generation anti-androgen for prostate cancer.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing quality of life questionnaires.
• Participants with serious or uncontrolled medical disorders that, in the opinion of the investigator, would impair the ability of the participant to receive protocol therapy or obscure the interpretation of AEs.
• Patients who are unable to swallow oral medications.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of acute myocardial infarction (AMI), cerebrovascular accident and/or coronary artery stent or bypass surgery within 6 months of study entry.
• Gastrointestinal disorders likely to interfere with absorption of the study medication.
• History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place.
• Uncontrolled hypertension despite medical management as indicated by systolic blood pressure \> 170 mm Hg or diastolic blood pressure \> 105 mm Hg at the screening visit. Patients may be re-screened after adjustments of anti- hypertensive medications.
• Inadequate organ function and laboratory tests as follows:
• WBC \< 2.0 x 109/L; Neutrophils \< 1.5 x 109/L; Platelets \<100x109/L; Hemoglobin \< 9.0 g/dL (no history of red blood cell transfusion within 4 weeks prior to study entry).

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead
• Bayer: collaborator

Study Sites (6)

Hospital São Rafael - Oncologia D'Or BA

Salvador, Estado de Bahia, 41.253-190, Brazil

Location

Hospital Sírio-Libanês DF

Brasília, Federal District, 70.200-730, Brazil

Location

CTTB - Centro de Tratamento de Tumores Botafogo (Oncoclínicas)

Rio de Janeiro, Rio de Janeiro, 22.250-905, Brazil

Location

HMV - Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90.035-000, Brazil

Location

Hospital Sírio-Libanês SP

São Paulo, São Paulo, 01.308-050, Brazil

Location

HIAE - Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05.653-000, Brazil

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

testosterone 17 beta-cypionate; darolutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Diogo Assed Bastos

  Latin American Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

• Pedro Henrique Isaacson Velho

  Latin American Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: September 22, 2020
• Study Start: June 9, 2021
• Primary Completion: March 15, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (6)