RECRUITING

Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer

Conditions

Prostate Cancer metastatic prostate cancer DFMO Enzalutamide High dose testosterone

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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

Asymptomatic patients with metastatic castrate resistant prostate cancer (mCRPC) without pain due to prostate cancer will be treated on an open label study to evaluate effectiveness of sequential treatment with the combination of difluoromethylornithine (DFMO) and high dose testosterone in sequence with enzalutamide to improve primary and secondary outcomes.

Official Title

Repeat Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Asymptomatic Patients With Metastatic Castration-Resistant Prostate Cancer: The APEX (Androgen and Polyamine Elimination Alternating With Xtandi) Trial

Quick Facts

Study Start:2023-10-04

Study Completion:2029-11-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06059118

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. 7. Must have had disease progression while on abiraterone acetate based on: * PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart And/ Or * Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or Prostate Cancer Working Group 3 (PCWG3) for patients with bone disease 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, 223Radium (Xofigo), Poly (ADP-ribose) polymerase (PARP) inhibitors, taxane chemotherapy, Lutetium prostate-specific membrane antigen (LuPSMA), antiandrogens (including enzalutamide, darolutamide, and apalutamide), and radiation is allowed if \>4 weeks from last dose. 11. Prior treatment with bipolar androgen therapy (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 abiraterone 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 transaminase (AST) (SGOT) and alanine transaminase (AST) (SGPT) \< 2.5 times ULN 15. Acceptable renal function: 16. Acceptable hematologic status: 1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L) 2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L) 3. Hemoglobin ≥ 8 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 DFMO and/or enzalutamide: * Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a longterm and persistent basis) and agree to remain abstinent. * Are sterilized (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); * Agree to use a male condom and have their partner use a contraceptive method with a failure rate of \<1% per year as described below when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant, and who agrees to the use of a condom by her partner. 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). 4. 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, severe and extensive spinal metastases with concern for spinal cord compression, extensive liver metastases). 5. Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if CD4+ T cell (a type of lymphocyte that helps coordinate the immune response against infection and disease) 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 (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 hepatitis C (HCV) infection are eligible if they have completed curative antiviral treatment and the HCV viral load is below the limit of quantification. 6. 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. 7. Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. \[Patients on enoxaparin are eligible for study. Patients on warfarin, rivaroxaban, or apixaban, who can be transitioned to enoxaparin prior to starting study treatments will be eligible\]. 8. Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation. 9. Hematocrit \>51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure \[per Endocrine Society Clinical Practice Guidelines (34)\] 10. Patients allergic to sesame seed oil or cottonseed oil are excluded. 11. Major surgery (i.e., requiring general anesthesia) 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. 12. Subjects with significant hearing loss defined as hearing loss that affects everyday life and/or for which a hearing aid is required. 13. Patients with history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation)

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.
7. Must have had disease progression while on abiraterone acetate based on:
* PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart And/ Or
* Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or Prostate Cancer Working Group 3 (PCWG3) for patients with bone disease
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, 223Radium (Xofigo), Poly (ADP-ribose) polymerase (PARP) inhibitors, taxane chemotherapy, Lutetium prostate-specific membrane antigen (LuPSMA), antiandrogens (including enzalutamide, darolutamide, and apalutamide), and radiation is allowed if \>4 weeks from last dose.
11. Prior treatment with bipolar androgen therapy (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 abiraterone 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 transaminase (AST) (SGOT) and alanine transaminase (AST) (SGPT) \< 2.5 times ULN
15. Acceptable renal function:
16. Acceptable hematologic status:
1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
3. Hemoglobin ≥ 8 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 DFMO and/or enzalutamide:
* Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a longterm and persistent basis) and agree to remain abstinent.
* Are sterilized (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate);
* Agree to use a male condom and have their partner use a contraceptive method with a failure rate of \<1% per year as described below when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant, and who agrees to the use of a condom by her partner.
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).
4. 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, severe and extensive spinal metastases with concern for spinal cord compression, extensive liver metastases).
5. Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if CD4+ T cell (a type of lymphocyte that helps coordinate the immune response against infection and disease) 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 (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 hepatitis C (HCV) infection are eligible if they have completed curative antiviral treatment and the HCV viral load is below the limit of quantification.
6. 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.
7. Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. \[Patients on enoxaparin are eligible for study. Patients on warfarin, rivaroxaban, or apixaban, who can be transitioned to enoxaparin prior to starting study treatments will be eligible\].
8. Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation.
9. Hematocrit \>51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure \[per Endocrine Society Clinical Practice Guidelines (34)\]
10. Patients allergic to sesame seed oil or cottonseed oil are excluded.
11. Major surgery (i.e., requiring general anesthesia) 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.
12. Subjects with significant hearing loss defined as hearing loss that affects everyday life and/or for which a hearing aid is required.
13. Patients with history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation)

Contacts and Locations

Study Contact

Laura Sena, MD, PhD

CONTACT

410-502-3825

laura.sena@jhmi.edu

Kathy Schultz, RN

CONTACT

410-614-9482

kschult3@jhmi.edu

Principal Investigator

Laura Sena, MD, PhD

PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Study Locations (Sites)

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Laura Sena, MD, PhD, 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 Date2023-10-04

Study Completion Date2029-11-30

Study Record Updates

Study Start Date2023-10-04

Study Completion Date2029-11-30

Terms related to this study

Keywords Provided by Researchers

prostate cancer
metastatic prostate cancer
DFMO
Enzalutamide
High dose testosterone

Additional Relevant MeSH Terms

Prostate Cancer