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

NCT06305598 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: I-3298823NCI-2024-01390
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Prostate Carcinoma; Castration-Resistant Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Incidence of adverse events

  Up to 30 days after end of treatment or progression

• Incidence of serious adverse events

  Up to 30 days after end of treatment or progression

• Prostate specific antigen (PSA) 50

  Up to 2 years after end of treatment/progression

• Measurable disease response

  Up to 2 years after end of treatment/progression

• Progression free survival

  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

Study Arms (1)

Treatment (Bipolar androgen therapy)

EXPERIMENTAL

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: Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Leuprolide Acetate; Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Drug: Testosterone Cypionate

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (Bipolar androgen therapy)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (Bipolar androgen therapy)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (Bipolar androgen therapy)

Leuprolide Acetate DRUG

Given SC

Also known as: A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Luprodex Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Lutrate, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur

Treatment (Bipolar androgen therapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (Bipolar androgen therapy)

Survey Administration OTHER

Ancillary studies

Treatment (Bipolar androgen therapy)

Testosterone Cypionate DRUG

Given IM

Also known as: depAndro, Depo-Testosterone, Depotest, Depovirin, Pertestis, Virilon

Treatment (Bipolar androgen therapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Prostate Cancer Foundation: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Biopsy; Leuprolide; luprolide acetate gel depot; Magnetic Resonance Spectroscopy; testosterone 17 beta-cypionate; Testosterone Propionate; Methyltestosterone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Spectrum Analysis; Chemistry Techniques, Analytical; Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Niraj Shenoy, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ASK RPCI

CONTACT

1-800-845-2300; askroswell@roswellpark.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: December 19, 2024
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)