Phase 2a Study of High-Dose Testosterone Followed by Radioligand Therapy in mCRPC

A Phase 2a Study of High Dose Testosterone Followed by Targeted Radioligand Therapy in Metastatic Castration Resistant Prostate Cancer

The purpose of this study is to evaluate whether high-dose testosterone followed by targeted radioligand therapy (TRT) is effective in treating metastatic castration resistant prostate cancer. Participants will be asked to spend about 6 months in this study. Participants will take study drug for 3.5 months.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Testosterone cypionate (Tc); Drug: ADT with Luteinizing hormone-releasing hormone (LHRH) analog; Drug: PSMA-617

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ashley Smith; Phone Number: 813-745-2937; Email: Ashley.Smith@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Sub-Investigator: Juskaran Chadha, DO
      • Principal Investigator: Jingsong Zhang, MD, PhD
      • Sub-Investigator: Aakash Patel, MD
      • Sub-Investigator: Jon Chatzkel, MD
      • Sub-Investigator: Ghazal (Gigi) Jameel, APRN
      • Sub-Investigator: Angel Johnson, APRN
      • Sub-Investigator: Tianshi (Mike) Liu, MD
      • Sub-Investigator: Sarah Mizelle, PA-C
      • Sub-Investigator: Aditi Patel, PA-C
      • Sub-Investigator: Alyssa Thompson, APRN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed prostate cancer that has progressed to mCRPC with no grade 2 or above cancer related symptoms.
• Participants need to have either PSA or imaging progression at castrate level of serum testosterone (i.e. <50ng/dl). The definition of PSA progression and the definitions of imaging progression on measurable or non-measurable lesions will be based on the prostate cancer working group 3 (PCWG3) criteria. Patients with symptomatic oligo progression (1-3 sites), the symptoms need to be improved to grade 1 or less with palliative local therapy prior to study enrollment.
• Participants need to have a positive PSMA PET scan and deem eligible for PSMA-617.
• Allowable prior therapies: Prior treatment with one line of ARPI. Patients need to be on ARPI for at least 4 weeks to be considered one line of therapy. Prior treatment with sipuleucel-T for mCRPC. Prior treatment with docetaxel in the castration sensitive setting.
• ECOG performance status 0-1.
• Participants must have adequate organ and marrow functions.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Participants with h/o myocardial infarction or history of congestive heart failure, need to have estimated left ventricle ejection fraction above 40% either on echocardiogram or MUGA scan within 6 months of study enrollment.
• Non-sterilized men who are sexually active with a female partner of childbearing potential treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 weeks after last dose of enzalutamide or docetaxel administration.
• Ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the subject's behalf. Stated willingness to comply with all study procedures and availability for the duration of the study.

Exclusion Criteria:

• Metastatic prostate cancer with known epidural, liver or brain metastases.
• No history of cord compression.
• Treatment with radiation within 30 days prior to the first dose of Tc400.
• Receiving any other investigation agents. Prior treatment with investigation agents need to have a washout period of 4 weeks prior to enrollment.
• Participants with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, delayed healing of wounds, ulcers, or bone fractures, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm: Tc400 followed by PSMA-617 (with continued ADT); Participants will receive Tc400 followed by PSMA-617, while continuing standard of care androgen deprivation therapy.	Drug: Testosterone cypionate (Tc); IM injection of Tc at 400 mg (Tc400) every 28 days for up to 3 doses.; Drug: ADT with Luteinizing hormone-releasing hormone (LHRH) analog; Continuing ADT with either surgical castration or chemical castration with LHRH analog is considered standard of care for mCRPC.; Drug: PSMA-617; IV at 7.4GBq (200mCi) once every 6 weeks for up to 6 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Tc400 and PSMA-617	Percentage of patients who can complete 3 doses of Tc400 followed by at least 2 doses of PSMA-617.	Up To 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in P/T ratio	Percentage of evaluable patients with 50% reduction in P/T ratio (PT50) compared to baseline P/T ratio based on PSA and testosterone values at screening.	Up To 6 Months
PSA50 and PSA 90	Percentage of patients who achieved PSA50 and PSA 90 responses after two doses of PSMA-617 compared to the pre PSMA-617 PSA values at day 60.	Up To 6 Months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Jingsong Zhang, MD, PhD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Androgen Antagonists; testosterone 17 beta-cypionate; Gonadotropin-Releasing Hormone; PSMA-617
• Other Study ID Numbers: MCC-23775

Drug and device information, study documents

• 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