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

NCT07476001 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-23775
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Reduction in P/T ratio

  Up To 6 Months

• PSA50 and PSA 90

  Up To 6 Months

Study Arms (1)

Single Arm: Tc400 followed by PSMA-617 (with continued ADT)

EXPERIMENTAL

Participants will receive Tc400 followed by PSMA-617, while continuing standard of care androgen deprivation therapy.

Drug: Testosterone cypionate (Tc); Drug: ADT with Luteinizing hormone-releasing hormone (LHRH) analog; Drug: PSMA-617

Interventions

Testosterone cypionate (Tc) DRUG

IM injection of Tc at 400 mg (Tc400) every 28 days for up to 3 doses.

Single Arm: Tc400 followed by PSMA-617 (with continued ADT)

ADT with Luteinizing hormone-releasing hormone (LHRH) analog DRUG

Continuing ADT with either surgical castration or chemical castration with LHRH analog is considered standard of care for mCRPC.

Single Arm: Tc400 followed by PSMA-617 (with continued ADT)

PSMA-617 DRUG

IV at 7.4GBq (200mCi) once every 6 weeks for up to 6 doses.

Single Arm: Tc400 followed by PSMA-617 (with continued ADT)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

MeSH Terms

Interventions

testosterone 17 beta-cypionate; Androgen Antagonists; Gonadotropin-Releasing Hormone; PSMA-617

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Jingsong Zhang, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley Smith

CONTACT

813-745-2937; Ashley.Smith@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: March 17, 2026
• Study Start: March 3, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

US (1)