Prostate Cancer
Conditions
Brief summary
The purpose of this phase II trial is to assess the clinical utility of clomiphene citrate for the augmentation of testosterone in prostate cancer survivors who complete androgen deprivation therapy (ADT), including the efficacy and tolerability of clomiphene, patient-reported quality of life outcomes, metabolic effects, biomarkers of response, and the oncologic safety of increasing testosterone. Up to 83 eligible participants who have completed radiation and ADT for non-metastatic prostate cancer will participate in this study. Participants are assigned to one of two cohorts: Cohort A is comprised intermediate-risk survivors who underwent short-course ADT (4-17 mo.) and are hypogonadal ≥6 months after ending ADT, and Cohort R is comprised of survivors who recovered to eugonadal levels of testosterone (≥ 300 ng/dL) within 6 months after ending ADT. Participants will be evaluated for clinical findings, toxicities, laboratory abnormalities (CBC, CMP, Lipid panel, Hgb A1C), changes to the hypothalamic-pituitary-gonadal axis (E2, LH, FSH, TT) \[dependent on Cohort\], biochemical recurrence (PSA), and quality of life (FACT-P, FACT-Fatigue, qADAM). Cohort R is an observational natural-recovery control group and will not be treated. Cohort A will be treated with oral clomiphene citrate, 25 mg, once daily for 6 months, then tested for persistence of response (eugonadal testosterone) after a 1-month washout period. After completing study assessments, participants will transition to standard survivorship follow-up. Thereafter, long-term health outcomes will be reviewed to determine the rates of biochemical recurrence and metastasis after 5 years.
Interventions
Oral clomiphene citrate, 25 mg, once daily for 6 months, then tested for persistence of response (eugonadal testosterone) after a 1-month washout period
Sponsors
University of Nebraska
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologic diagnosis of adenocarcinoma of the prostate 2. No evidence of metastatic disease 3. Prior definitive local therapy with radiation 4. Prior definitive continuous ADT 4-17 months in duration (treatment may include abiraterone). 5. Available serum testosterone measurement. Testosterone \< 300 ng/dL is required for inclusion in Cohort A; testosterone ≥300 ng/dL is required for inclusion in Cohort R. 6. PSA \<0.1 7. ECOG performance status \< 3 8. Prior pre-treatment staging (bone and soft tissue imaging) that ruled out metastatic disease
Exclusion criteria
1. Known hypogonadism prior to initiation of ADT 2. Prior prostatectomy 3. Known endocrine or liver dysfunction 4. Polycythemia 5. Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia 6. Known intracranial tumor 7. Psychiatric illness/social situations or geographical condition that would limit compliance with study requirements 8. Use of clomiphene citrate, testosterone, or other hormone replacement therapy 9. Recent (within the last 3 months) venous thromboembolism 10. Severe lower urinary tract symptoms 11. Use of inhibitors or inducers of CYP2D6 12. Symptoms suggestive of recurrent or metastatic disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the proportion of participants with eugonadal serum testosterone (≥ 300 ng/dL). | 6 Months |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the change in total testosterone as indicated by change from serum testosterone at baseline through end of study (EOS). | 8 years |
Countries
United States
Contacts
CONTACTIIT Office
PRINCIPAL_INVESTIGATORBenjamin Teply, MD
University of Nebraska
Outcome results
None listed