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Safety and Efficacy of Oral Testosterone Undecanoate Followed by Enzalutamide as Therapy for Men With Metastatic Castrate Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05081193
Recruitment Status : Recruiting
First Posted : October 18, 2021
Last Update Posted : May 12, 2022
Sponsor:
Collaborator:
Clarus Therapeutics
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

Previous studies of high dose testosterone therapy given intramuscularly to men with metastatic castrate resistant prostate cancer suggest that high serum levels of testosterone may be required for clinical response. This injection regimen was given as one dose of 400mg injection every 28 days, which initially produces high serum testosterone levels but these levels drop to a varying degree in some men over the 28-day cycle.

In this 30 patient trial will analyze the effects of oral testosterone therapy in men with metastatic castrate resistant prostate cancer taken on a schedule of seven days of oral testosterone therapy followed by seven days of no therapy for a twenty-eight day cycle. This therapy will be given for three 28 day cycles consecutively followed by radiographic scans to evaluate the metastatic disease. Patients will be allowed to continue on this therapy until the patients show signs of radiographic progression. If the patients show signs of radiographic progression after the first three cycles, the patients will stop taking the oral testosterone therapy and begin taking enzalutamide therapy. Enzalutamide therapy will be taken for three 28 day cycles, then radiographic scans will be taken. If there are no signs of radiographic progression, patients can continue to take enzalutamide therapy for an additional 3 cycles while on study. Patients with continued PSA or objective response will come off study but continue on enzalutamide as standard of care therapy.

This study will help the investigators to understand if treating these men with the highest FDA approved dose of oral testosterone therapy will achieve similar and sustained high levels of serum testosterone that will produce similar or enhanced therapeutic response to the therapy when compared to the serum testosterone levels found in the previous injection therapy trials.


Condition or disease Intervention/treatment Phase
Prostate Cancer Castration-resistant Prostate Cancer Metastatic Castration-resistant Prostate Cancer Drug: Testosterone Undecanoate Drug: Enzalutamide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Oral Testosterone Therapy-396 mg given twice per day on days 1-7 and 15-21 of a 28 day cycle until radiographic progression. After a 21 day washout period, Enzalutamide therapy given at 160 mg once daily will be taken for a maximum of 6 cycles while on study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Assessing the Safety and Efficacy of Oral Testosterone Undecanoate Followed by Enzalutamide as Therapy for Men With Metastatic Castrate Resistant Prostate Cancer
Actual Study Start Date : March 7, 2022
Estimated Primary Completion Date : December 30, 2025
Estimated Study Completion Date : December 30, 2027


Arm Intervention/treatment
Experimental: Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide Therapy
Oral Testosterone Therapy-396 mg given twice per day on days 1-7 and 15-21 of a 28 day cycle until radiographic progression. After a 21 day washout period, Enzalutamide therapy given at 160 mg once daily will be taken for a maximum of 6 cycles while on study.
Drug: Testosterone Undecanoate
198mg taken twice daily
Other Name: Jatenzo

Drug: Enzalutamide
160mg taken once daily
Other Name: Xtandi




Primary Outcome Measures :
  1. Objective Response Rate of Oral Testosterone Undecanoate (CT Scan) [ Time Frame: Up to 2 years ]
    Radiographic responses to Oral Testosterone therapy using CT scan measurements. Radiographic progression is assessed by RECIST (Response Evaluation Criteria in Solid Tumors). Per RECIST, progression is defined as ≥ 20% and ≥ 5 mm from nadir of the sum of the diameters of target lesions.


Secondary Outcome Measures :
  1. PSA50 Response to Oral Testosterone Therapy [ Time Frame: 2 years ]
    Number of participants with PSA50 response to Oral Testosterone therapy defined as at least a 50% decline in Prostate Specific Antigen (PSA) from baseline value.

  2. Time to PSA Progression While on Oral Testosterone [ Time Frame: Up to 2 years ]
    Number of weeks from baseline until PSA progression.

  3. Time to Clinical or Radiographic Progression While on Oral Testosterone [ Time Frame: Up to 2 years ]
    Number of weeks from baseline until radiographic or clinical progression, whichever comes first. Radiographic progression is assessed by Response Evaluation Criteria in Solid Tumors (RECIST) and Prostate Cancer Working Group 3 (PCWG3) criteria. Per RECIST, progression is defined as ≥ 20% and ≥ 5 mm from nadir of the sum of the diameters of target lesions. Per PCWG3 criteria, radiographic progression is defined as ≥ 20% sum of the longest diameter of target lesions, or ≥ 2 new lesions on bone scan from baseline. Clinical progression is defined as new spinal cord or nerve root compression, new pathologic fracture or use of opioid analgesics for cancer-related pain.

  4. PSA50 Response to Enzalutamide Therapy [ Time Frame: 2 years ]
    Number of participants with PSA50 response to enzalutamide therapy defined as at least a 50% decline in Prostate Specific Antigen (PSA) from baseline value.

  5. Objective Response Rate of Enzalutamide Therapy (CT Scan) [ Time Frame: 2 years ]
    Radiographic responses to Enzalutamide therapy using CT scan measurements after 3 cycles and after 6 cycles of therapy. Radiographic progression is assessed by RECIST (Response Evaluation Criteria in Solid Tumors) criteria ). Per RECIST, progression is defined as ≥ 20% and ≥ 5 mm from nadir of the sum of the diameters of target lesions.

  6. Peak Testosterone Level [ Time Frame: At 4 hours post first dose ]
    Mean peak testosterone level (ng/dL) measured at 4 hours post first dose of oral testosterone therapy.

  7. Trough Testosterone Level [ Time Frame: Up to 96 hours after cycle 1 day 7 dose ]
    Mean trough testosterone level (ng/dL) measured within 24, 48, 72 or 96 hours after cycle 1 day 7 dose of oral testosterone therapy

  8. PBMC Immunologic and metabolic phenotype [ Time Frame: 2 years ]
    Phenotype of peripheral blood mononucleated cell (PBMC) as defined by number of cluster of differentiation 4 (CD4) Tcells, cluster of differentiation 8 (CD8) Tcells, FOXP3+ Treg cells, B cells, Natural Killer (NK) cells, monocytes, dendritic cells, and myeloid derived suppressor cells. PBMCs will be immunophenotyped using multiparameter flow cytometry.

  9. Change in Quality of Life as Assessed by the-FACIT-Fatigue Questionnaire [ Time Frame: 2 years ]
    The Functional Assessment of Chronic Illness Therapy - Fatigue has a score range of 0-52 with higher scores indicating better quality of life.

  10. Change in Quality of Life as Assessed by the- Short Form 36 (SF-36) Questionnaire [ Time Frame: 2 years ]
    All questions are scored on a scale from 0 to 100. The total score from all of the questions answered is divided by the total number of the questions answered yielding a global score from 0-100 with 100 representing the highest level of functioning possible.

  11. Safety of Trial Therapy as assessed by adverse event reporting [ Time Frame: 2 years ]
    Safety as assessed by adverse event reporting. Grading of adverse events will be done by utilizing the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Determination of relationship of the adverse event to the study procedures or study drug will be performed by the PI using the standard attribution terminology (e.g. unrelated, possibly related, etc.).

  12. Tolerability of Trial Therapy as assessed by adverse event reporting [ Time Frame: 2 years ]
    Tolerability as assessed by adverse event reporting. Grading of adverse events will be done by utilizing the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Determination of relationship of the adverse event to the study procedures or study drug will be performed by the PI using the standard attribution terminology (e.g. unrelated, possibly related, etc.).

  13. Time to PSA Progression While on Enzalutamide [ Time Frame: Up to 2 years ]
    Number of weeks from start of enzalutamide treatment until PSA progression.

  14. Time to PSA Progression While on Enzalutamide from Start of Oral Testosterone Therapy [ Time Frame: Up to 2 years ]
    Number of weeks from start of oral testosterone therapy until PSA progression while on enzalutamide treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has the ability to understand and willingness to sign a written informed consent document.
  • Patient is a male aged 18 years or older.
  • Patient has histologically-confirmed adenocarcinoma of the prostate
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 (as defined in Appendix A: Performance Status Criteria;
  • Patient has evidence of metastatic, measurable disease by CT scan. Measurable disease is defined by RECIST 1.1 as at least one measurable lesion ≥10mm by CT scan
  • Patient is progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist)
  • Patient has documented castrate level of serum testosterone (<50 ng/dl)
  • Patient is progressing on luteinizing hormone-releasing hormone (LHRH) agonist/antagonist plus anti-androgen or abiraterone for CSPC. (Note: Must be off anti-androgen or abiraterone for 4 weeks prior to first treatment with OT.) LHRH (luteinizing hormone-releasing hormone)
  • Patient has had prior docetaxel for CSPC. Note: Docetaxel is permitted if ≤ 6 doses were given in conjunction with first-line androgen deprivation therapy and >6 months since last dose of docetaxel. (CSPC-castrate sensitive prostate cancer)
  • Patient is currently taking prednisone and cannot be weaned entirely off. Note: Patient's dose must be maintained on lowest stable dose that relieves symptoms. Patient is receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone if possible prior to starting OT.
  • Patient has had a rising PSA on two successive measurements at least two weeks apart.
  • Patient agrees to continue on castrating therapy throughout OT treatment.
  • Patient's screening lab values are within the following parameters:

    1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
    2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
    3. Hemoglobin ≥ 9 g/dL
    4. Serum creatinine < 2.5 times ULN
    5. Bilirubin < 2.5 times institutional upper limit of normal (ULN)
    6. Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 times ULN
  • Patient has had surgery, has completed at least 4 weeks of recovery and has no persistent toxicity > grade 1.

Exclusion Criteria:

  • Patient has pain due to metastatic prostate cancer requiring opioid analgesics.
  • Patient has had prior treatment with any agent for metastatic castration-resistant prostate cancer. (Includes docetaxel, cabazitaxel, anti-androgen, abiraterone, or investigational agents)
  • Patient requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia. Note: Patients with indwelling catheter/suprapubic catheter to relieve obstruction are eligible.
  • Patient has 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, epidural spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction).
  • Patient has 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, epidural spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction).
  • Patient has active uncontrolled infection, such as HIV/AIDS or chronic hepatitis B or untreated chronic hepatitis C.
  • Patient has had prior history of a thromboembolic event within the past two years and not currently on systemic anticoagulation.
  • Patient is on Coumadin. Note: If anticoagulation therapy is mandatory, patient must be switched to an alternative medication) 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 enoxaparin prior to starting study treatments, will be eligible.
  • Patient has hematocrit >50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines].

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05081193


Contacts
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Contact: Samuel Denmeade, MD 410-955-8875 denmesa@jhmi.edu
Contact: Rana Sullivan, RN 410-614-6337 tomalra@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21231
Contact: Samuel Denmeade, MD    410-955-8875    denmesa@jhmi.edu   
Contact: Rana Sullivan, RN    410-614-6337    tomalra@jhmi.edu   
Principal Investigator: Samuel Denmeade, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Clarus Therapeutics
Investigators
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Principal Investigator: Samuel Denmeade, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT05081193    
Other Study ID Numbers: J2178
IRB00284702 ( Other Identifier: Johns Hopkins Medicine )
First Posted: October 18, 2021    Key Record Dates
Last Update Posted: May 12, 2022
Last Verified: May 2022

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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.: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Oral Testosterone Therapy
Enzalutamide
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Methyltestosterone
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents