High-dose testosterone followed by PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer
A Phase 2a Study of High Dose Testosterone Followed by Targeted Radioligand Therapy in Metastatic Castration Resistant Prostate Cancer
This trial tests whether short-term high-dose testosterone followed by a PSMA-targeted radioligand (PSMA-617) can help men with metastatic castration-resistant prostate cancer that is progressing on castrate-level testosterone.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 12 (estimated) |
| Ages | 18 Years and up |
| Sex | Male |
| Sponsor | H. Lee Moffitt Cancer Center and Research Institute Academic / other |
| Drugs / interventions | radiation |
| Locations | 1 site (Tampa, Florida) |
| Trial ID | NCT07476001 on ClinicalTrials.gov |
What this trial studies
This Phase 2a interventional trial gives participants high-dose testosterone (testosterone cypionate) for about 3.5 months while keeping them on androgen-deprivation therapy, followed by PSMA-617 targeted radioligand therapy for PSMA-positive tumors. Eligible participants must have mCRPC with biochemical or imaging progression at castrate serum testosterone and a positive PSMA PET scan. The protocol allows prior one line of androgen receptor pathway inhibitor and certain prior chemo or sipuleucel-T as specified. Participants are followed for roughly six months to measure tumor response, safety, and treatment tolerability.
Who should consider this trial
Good fit: Ideal candidates are men with histologically confirmed metastatic castration-resistant prostate cancer who have PSA or imaging progression at castrate testosterone, a positive PSMA PET scan, limited or managed symptoms, and allowed prior therapies such as one line of ARPI.
Not a fit: Patients who are PSMA-PET negative, have uncontrolled or high-grade cancer symptoms, or have disease features outside the trial's eligibility are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could improve tumor control and extend the time before further progression by increasing PSMA expression and improving delivery of PSMA-targeted radioligand therapy.
How similar studies have performed: Preclinical data and small clinical reports suggest testosterone can increase PSMA expression and may sensitize tumors to PSMA-directed therapies, but combining high-dose testosterone followed by PSMA-617 remains an experimental approach with limited clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Tampa, Florida
- Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
Study contacts
- Principal investigator: Jingsong Zhang, MD, PhD — Moffitt Cancer Center
- Study coordinator: Ashley Smith
- Email: Ashley.Smith@moffitt.org
- Phone: 813-745-2937
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.