RECRUITING

The COSMYC Trial (COmbined Suppression of MYC)

Conditions

Metastatic Castration-resistant Prostate Cancer Prostate Cancer ZEN-3694 Bipolar androgen therapy testosterone cypionate enzalutamide

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This research is being done to determine if receiving the combination of testosterone and ZEN-3694 followed by the combination of enzalutamide plus ZEN-3694 will decrease the size of tumors in patients with prostate cancer that has become resistant to castration and other therapies. The investigators also want to determine if dosing first with the combination of testosterone and ZEN-3694 may cause enzalutamide and ZEN-3694 to work more effectively.

Official Title

A Phase II Study of Sequential Bipolar Androgen Therapy and ZEN-3694 in Sequence With Enzalutamide + ZEN-3694 in Asymptomatic Patients With Metastatic CRPC: The COSMYC Trial (COmbined Suppression of MYC)

Quick Facts

Study Start:2025-08-19

Study Completion:2031-08-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06922318

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Eastern Cooperative Oncology Group (ECOG) Performance status ≤2. 2. Age ≥18 years. 3. Histologically-confirmed adenocarcinoma of the prostate. 4. Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist). 5. Documented castrate level of serum testosterone (\<50 ng/dl). 6. Metastatic disease radiographically documented by CT or bone scan. While CT scan is preferred, Prostate-Specific Membrane Antigen (PSMA) scan (e.g. Pylarify) may be substitute for CT scan if evidence of metastatic disease observed on the CT portion of the PSMA scan. 7. Must have had disease progression while on a second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) based on: 8. Screening PSA must be ≥ 1.0 ng/mL. 9. Patients with soft tissue lesion amenable to biopsy must agree to biopsy collection pre-treatment and at a defined point on treatment to perform tumor tissue analysis. 10. Prior treatment with Provenge vaccine, 223 Radium (Xofigo), poly(ADP-ribose) polymerase (PARP) inhibitors, taxane chemotherapy, Pluvicto, antiandrogens (including enzalutamide, darolutamide, and apalutamide), and radiation is allowed if \>4 weeks from last dose. 11. Prior treatment with BAT is allowed if the patient has progressed on an AR-axis inhibitor (i.e. abiraterone or antiandrogen) since BAT treatment. 12. Patients must be withdrawn from second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) for ≥ 2 weeks. 13. Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period. 14. Acceptable liver function: 1. Bilirubin \< 2.5 times institutional upper limit of normal (ULN) 2. Aspartate Transferase (AST) (SGOT) and Alanine Transaminase (ALT) (SGPT) \< 2.5 times ULN 15. Acceptable renal function: 16. Acceptable hematologic status: 1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 (1.5 ×109/L) 2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L) 3. Hemoglobin ≥ 7.5 g/dL. 17. Ability to understand and willingness to sign a written informed consent document. 18. Sexually active participants with female partners of childbearing potential are eligible to participate if they agree to follow 1 of the following methods of contraception consistently, starting from screening, during the study and for at least 3 months after the last dose of ZEN-3694 and/or enzalutamide: 19. Sexually active participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse; or use a male condom during each episode of penile penetration during the study 20. Patients with soft-tissue disease amenable to biopsy as determined by Interventional Radiology must agree to serial biopsies as per the study schedule to be eligible.	1. Pain due to metastatic prostate cancer requiring treatment intervention with opioid pain medication. 2. ECOG Performance status ≥3 3. Requirement for urinary self-catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH). Patients with indwelling Foley or suprapubic catheter for obstructive symptoms are eligible. 4. Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if cluster of differentiation 4 (CD4)+ T cell counts are ≥ 350 cell/ul, they have had no opportunistic infection within the past 12 months, they have been on established antiretroviral therapy (ART) for at least four weeks, the HIV viral load is less than 400 copies/ml prior to enrollment, and there is no significant drug-drug interaction with ART and the study drugs. Patients with chronic hepatitis B virus (HBV) infection with active disease who meet criteria for anti HBV therapy are eligible if they are on a suppressive antiviral therapy prior to enrollment and there is no drug-drug interaction with the study drugs. Patients with a history of HCV infection are eligible if they have completed curative antiviral treatment and the hepatitis C virus (HCV) viral load is below the limit of quantification. 5. Any condition or mental impairment that may compromise the ability to give informed consent, patient's safety or compliance with study requirements as determined by the investigator. 6. Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. \[Patients on enoxaparin or edoxaban are eligible for study. Patients on warfarin, rivaroxaban, or apixaban, who can be transitioned to one of these alternative agents prior to starting study treatments will be eligible\]. 7. Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation. 8. Hematocrit \>51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure \[per Endocrine Society Clinical Practice Guidelines (34)\] 9. Patients allergic to sesame seed oil or cottonseed oil are excluded. 10. Major surgery (i.e. as defined by treating physician) within 3 weeks before screening, or has not fully recovered from prior surgery (i.e., unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.

Inclusion Criteria

Exclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) Performance status ≤2.
2. Age ≥18 years.
3. Histologically-confirmed adenocarcinoma of the prostate.
4. Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist).
5. Documented castrate level of serum testosterone (\<50 ng/dl).
6. Metastatic disease radiographically documented by CT or bone scan. While CT scan is preferred, Prostate-Specific Membrane Antigen (PSMA) scan (e.g. Pylarify) may be substitute for CT scan if evidence of metastatic disease observed on the CT portion of the PSMA scan.
7. Must have had disease progression while on a second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) based on:
8. Screening PSA must be ≥ 1.0 ng/mL.
9. Patients with soft tissue lesion amenable to biopsy must agree to biopsy collection pre-treatment and at a defined point on treatment to perform tumor tissue analysis.
10. Prior treatment with Provenge vaccine, 223 Radium (Xofigo), poly(ADP-ribose) polymerase (PARP) inhibitors, taxane chemotherapy, Pluvicto, antiandrogens (including enzalutamide, darolutamide, and apalutamide), and radiation is allowed if \>4 weeks from last dose.
11. Prior treatment with BAT is allowed if the patient has progressed on an AR-axis inhibitor (i.e. abiraterone or antiandrogen) since BAT treatment.
12. Patients must be withdrawn from second-generation AR-axis inhibitor (Abiraterone, Enzalutamide, Darolutamide, or Apalutamide) for ≥ 2 weeks.
13. Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period.
14. Acceptable liver function:
1. Bilirubin \< 2.5 times institutional upper limit of normal (ULN)
2. Aspartate Transferase (AST) (SGOT) and Alanine Transaminase (ALT) (SGPT) \< 2.5 times ULN
15. Acceptable renal function:
16. Acceptable hematologic status:
1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 (1.5 ×109/L)
2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
3. Hemoglobin ≥ 7.5 g/dL.
17. Ability to understand and willingness to sign a written informed consent document.
18. Sexually active participants with female partners of childbearing potential are eligible to participate if they agree to follow 1 of the following methods of contraception consistently, starting from screening, during the study and for at least 3 months after the last dose of ZEN-3694 and/or enzalutamide:
19. Sexually active participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse; or use a male condom during each episode of penile penetration during the study
20. Patients with soft-tissue disease amenable to biopsy as determined by Interventional Radiology must agree to serial biopsies as per the study schedule to be eligible.

1. Pain due to metastatic prostate cancer requiring treatment intervention with opioid pain medication.
2. ECOG Performance status ≥3
3. Requirement for urinary self-catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH). Patients with indwelling Foley or suprapubic catheter for obstructive symptoms are eligible.
4. Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if cluster of differentiation 4 (CD4)+ T cell counts are ≥ 350 cell/ul, they have had no opportunistic infection within the past 12 months, they have been on established antiretroviral therapy (ART) for at least four weeks, the HIV viral load is less than 400 copies/ml prior to enrollment, and there is no significant drug-drug interaction with ART and the study drugs. Patients with chronic hepatitis B virus (HBV) infection with active disease who meet criteria for anti HBV therapy are eligible if they are on a suppressive antiviral therapy prior to enrollment and there is no drug-drug interaction with the study drugs. Patients with a history of HCV infection are eligible if they have completed curative antiviral treatment and the hepatitis C virus (HCV) viral load is below the limit of quantification.
5. Any condition or mental impairment that may compromise the ability to give informed consent, patient's safety or compliance with study requirements as determined by the investigator.
6. Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. \[Patients on enoxaparin or edoxaban are eligible for study. Patients on warfarin, rivaroxaban, or apixaban, who can be transitioned to one of these alternative agents prior to starting study treatments will be eligible\].
7. Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation.
8. Hematocrit \>51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure \[per Endocrine Society Clinical Practice Guidelines (34)\]
9. Patients allergic to sesame seed oil or cottonseed oil are excluded.
10. Major surgery (i.e. as defined by treating physician) within 3 weeks before screening, or has not fully recovered from prior surgery (i.e., unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.

Contacts and Locations

Study Contact

Samuel Denmeade, MD

CONTACT

410-733-3232

denmesa@jhmi.edu

Sin Chan, MS

CONTACT

410-614-3630

schan44@jhmi.edu

Principal Investigator

Samuel Denmeade, MD

PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Study Locations (Sites)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21205

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Samuel Denmeade, MD, PRINCIPAL_INVESTIGATOR, Johns Hopkins University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08-19

Study Completion Date2031-08-30

Study Record Updates

Study Start Date2025-08-19

Study Completion Date2031-08-30

Terms related to this study

Keywords Provided by Researchers

Prostate Cancer
ZEN-3694
Bipolar androgen therapy
testosterone cypionate
enzalutamide

Additional Relevant MeSH Terms

Metastatic Castration-resistant Prostate Cancer