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

  • End date
    Apr 18, 2024
  • participants needed
  • sponsor
    Latin American Cooperative Oncology Group
Updated on 18 December 2021


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).


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) progressing after abiraterone. Extreme androgen therapy will include alternating 56-day cycles of darolutamide 1,200mg/day (two 300 tablets every 12 hours) p.o. for 28 days followed by testosterone cypionate 400 mg i.m. During the treatment period, patients will be followed with chest, abdomen and pelvis CT and bone scan every 8-9 weeks until cycle 4 and every 12 weeks thereafter during the study period. Patients who present with disease progression but are considered to be benefiting from the treatment may continue receiving it, but will be followed by their treating physician according to local guidelines (follow-up period). All patients who stopped treatment will enter follow-up period and survival data will be collected from medical charts. Additionally, QoL questionnaires (BPI-SF, EQ-5D-3L and FACT-P) will be applied every 8-9 weeks until the end of treatment.

Condition Prostate Cancer
Treatment Testosterone cypionate, Darolutamide
Clinical Study IdentifierNCT04558866
SponsorLatin American Cooperative Oncology Group
Last Modified on18 December 2021


Yes No Not Sure

Inclusion Criteria

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 castration-resistant disease up to 28 days (± 7 days) prior to study arm assignment without prior enzalutamide, and are not candidates for or refuse immediate chemotherapy
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
Sufficient tumor tissue obtained prior to enrollment from a metastatic tumor lesion or from a primary tumor lesion (formalinfixed paraffin-embedded [FFPE] block or unstained tumor tissue sections). Tumor sample may be from core biopsy, punch biopsy, excisional biopsy, or surgical specimen)

Exclusion Criteria

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, such as a condition associated with frequent diarrhea
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 seizure or any condition that may have a predisposition to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit)
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 as indicated by systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at the screening visit
Adequate organ function and laboratory tests as follows
WBC < 2000/μL; Neutrophils < 1500/uL; Platelets <100x103/uL; Hemoglobin < 9.0 g/dL
Serum creatinine > 2x ULN unless creatinine clearance ≥ 40 mL/min (measured or calculated using the Cockroft-Gault formula)
AST/ALT: > 3.0 x ULN; Total bilirubin >1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0x ULN)
History of allergy or hypersensitivity to study drug components
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