Bipolar Androgen Therapy to Restore Sensitivity to Androgen Deprivation Therapy for Patients With Metastatic Castration Resistant Prostate Cancer

Bipolar Androgen Therapy in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This phase I trial tests the change in androgen receptor sensitivity, side effects and effectiveness of bipolar androgen therapy, using testosterone, in patients with castration resistant prostate cancer that has spread to other places is the body (metastatic). Bipolar androgen therapy is the regulation of testosterone between castration levels (lower than what would be normally present) and supraphysiological levels (amounts greater than normally found in the body). This may suppress cancer cell growth, which reduces prostate-specific antigen (PSA) levels and may delay cancer progression.

Study Overview

• Status: Recruiting
• Conditions: Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Bone Scan; Drug: Testosterone Cypionate; Drug: Leuprolide Acetate

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the influence of bipolar androgen therapy (BAT) on androgen receptor (AR) activity in patients with metastatic castration-resistant prostate cancer (mCRPC).

SECONDARY OBJECTIVES:

• To determine the clinical efficacy and safety of BAT in patients with mCRPC.
• To determine the change in fatigue and quality of life in patients receiving BAT.

OUTLINE:

Patients receive testosterone intramuscularly (IM) on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate subcutaneously (SC) per their standard schedule. Patients undergo computed tomography (CT) scan, bone scan and may undergo magnetic resonance imaging and tumor biopsy throughout the study.

After completion of study treatment, patients follow up at 30 days and every 3 months for up to 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ASK RPCI; Phone Number: 1-800-845-2300; Email: askroswell@roswellpark.org

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Principal Investigator: Niraj Shenoy
      • Contact: Saby George, MD; Phone Number: 716-845-8313; Email: Saby.George@roswellpark.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years of age
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Histologically confirmed carcinoma of the prostate
• Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist)
• Documented castrate level of blood testosterone (< 50 ng/dL)
• Patients must have progressed on prior treatment with at least one Androgen Receptor Signaling Inhibitors (ARSI) (by prostate specific antigen [PSA] criteria or radiographically)
• Have biopsiable disease (a fresh biopsy is not required at baseline if adequate archival tissue is available)
• Absolute neutrophil count: ≥1,200/µL
• Platelets: ≥ 100,000/µL
• Total bilirubin: ≤ 1.2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): ≤ 3 × institutional ULN
• Creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault equation)
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Greater than 5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤ 1 cm in diameter is permitted)
• 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)
• Active uncontrolled infection, including known history of acquired immunodeficiency syndrome (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 12 months 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)
• 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
• Known allergy to testosterone cypionate or any of its excipients
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (Bipolar androgen therapy); Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Other: Survey Administration; Ancillary studies; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Drug: Testosterone Cypionate; Given IM; Other Names: Depo-Testosterone; depAndro; Depotest; Depovirin; Pertestis; Virilon; Drug: Leuprolide Acetate; Given SC; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Lutrate; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur; Luprodex Depot

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Androgen receptor (AR) activity	Assessed with spatial transcriptomic profiling using the well-validated Nelson 10 genes signature AR score. Will be summarized by timepoint using the mean and standard deviation, and graphically using dot-plots. The mean pre/post-intervention levels will be compared using a one-sided paired t-test (expected increase); with the effect summarized using the mean difference and fold change.	Up to 2 years after end of treatment/progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Up to 30 days after end of treatment or progression
Incidence of serious adverse events	Using the NCI CTCAE version 5.0.	Up to 30 days after end of treatment or progression
Prostate specific antigen (PSA) 50	Defined as the proportion of patients with a >=50% reduction in PSA from the maximal PSA level achieved during the treatment. Will be summarized using frequencies and relative frequencies.	Up to 2 years after end of treatment/progression
Measurable disease response	Will be summarized using frequencies and relative frequencies.	Up to 2 years after end of treatment/progression
Progression free survival	Will be summarized using standard Kaplan-Meier methods, where the medians will be estimated with 95% confidence intervals (CIs).	From day 1 of treatment to the date when the first site of disease is found to progress, assessed up to 2 years after end of treatment/progression
Overall survival	Will be summarized using standard Kaplan-Meier methods, where the medians will be estimated with 95% CIs.	From the time of initiation of treatment until death from any cause, assessed up to 2 years after end of treatment/progression
Assess Quality of life	Using the FACIT-F.he FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials. It consists of 27 general QOL questions divided into 4 domains (physical, social, emotional, and functional), plus a 13-item fatigue sub-score. The patient rates the intensity of fatigue and its related symptoms on a scale of 0-4. The total score ranges between 0 and 52, with higher scores denoting less fatigue . Comparisons will be made between pre- and post-treatment using a paired t-test.	Up to 2 years after end of treatment/progression
Assess Quality of Life	A self-reported 36 item survey (SF-36) of patient health where higher scores indicated better health related quality of life	Up to 2 years after end of treatment/progression
Assess Fatigue	Using the FACIT-F (FACIT Fatigue Scale) the FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials. It consists of 27 general QOL questions divided into 4 domains (physical, social, emotional, and functional), plus a 13-item fatigue sub-score. The patient rates the intensity of fatigue and its related symptoms on a scale of 0-4. The total score ranges between 0 and 52, with higher scores denoting less fatigue	Up to 2 years after end of treatment/progression
Assess change in Fatigue	Assess changes in Fatigue using the SF-36 (Short Form Health Survey) A self reported 36 item survey where lower scores indicate greater fatigue.	Up to 2 years after end of treatment/progression

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Prostate Cancer Foundation
• Investigators: Principal Investigator: Saby George, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): December 15, 2029
• Study Completion (Estimated): December 15, 2029

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Gonadal Steroid Hormones; Gonadal Hormones; Androstenes; Androstanes; Androstenols; Testosterone Congeners; Gonadotropin-Releasing Hormone; Testosterone; Methyltestosterone; Leuprolide; testosterone 17 beta-cypionate; luprolide acetate gel depot; Biopsy; Magnetic Resonance Spectroscopy; Testosterone Propionate
• Other Study ID Numbers: I-3298823 (Other Identifier: Roswell Park Cancer Institute); NCI-2024-01390 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes