HRT-PC Trial: Hormone Recovery After Treatment for Prostate Cancer Trial. An Open-label Phase II Study of Clomiphene Citrate in Patients With Persistent Hypogonadism After ADT for Treatment of Localized Prostate Cancer

NCT07882862 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HRTPC
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the proportion of participants with eugonadal serum testosterone (≥ 300 ng/dL).

  6 Months

Secondary Outcomes (1)

• To evaluate the change in total testosterone as indicated by change from serum testosterone at baseline through end of study (EOS).

  8 years

Study Arms (2)

Cohort A - oral clomiphene citrate, 25 mg, once daily for 6 months

EXPERIMENTAL

Drug: Clomiphene Citrate 25mg

Cohort R is an observational natural-recovery control group and will not be treated

NO INTERVENTION

Interventions

Clomiphene Citrate 25mg DRUG

Oral clomiphene citrate, 25 mg, once daily for 6 months, then tested for persistence of response (eugonadal testosterone) after a 1-month washout period

Cohort A - oral clomiphene citrate, 25 mg, once daily for 6 months

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of adenocarcinoma of the prostate
• No evidence of metastatic disease
• Prior definitive local therapy with radiation
• Prior definitive continuous ADT 4-17 months in duration (treatment may include abiraterone).
• PSA \<0.1
• ECOG performance status \< 3
• Prior pre-treatment staging (bone and soft tissue imaging) that ruled out metastatic disease

You may not qualify if:

• Known hypogonadism prior to initiation of ADT
• Prior prostatectomy
• Known endocrine or liver dysfunction
• Polycythemia
• Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Known intracranial tumor
• Psychiatric illness/social situations or geographical condition that would limit compliance with study requirements
• Use of clomiphene citrate, testosterone, or other hormone replacement therapy
• Recent (within the last 3 months) venous thromboembolism
• Severe lower urinary tract symptoms
• Use of inhibitors or inducers of CYP2D6
• Symptoms suggestive of recurrent or metastatic disease

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University if Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Clomiphene

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)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Benjamin Teply, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

IIT Office

CONTACT

402-559-4596; iitoffice@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2026
• First Posted: October 20, 2026
• Study Start (Estimated): January 31, 2027
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): January 31, 2037
• Last Updated: October 20, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)