Randomized Phase II Trial of Targeted Radiation With no Castration for Mcrpc

About This Trial

This clinical trial is for men with advanced prostate cancer that has spread to bones or other tissues and is no longer responding to standard hormone-blocking therapies.
Researchers are testing whether combining two forms of precise, targeted radiation—one delivered from outside the body and one injected into the bloodstream—can effectively control the disease.
What makes this study unique is that all participants will stop taking their usual testosterone-lowering treatments during the radiation therapy.
After radiation is complete, half of the participants will be randomly chosen to receive testosterone replacement therapy to see if restoring hormone levels helps, while the other half will not.

More Information

This trial tests if the combination of comprehensive metastasis directed therapy delivered by a precision form of external beam radiotherapy (stereotactic ablative radiotherapy), combined with PSMA targeted radiopharmaceutical therapy and cessation of castration, and then followed by testosterone replacement, is an effective treatment for metastatic castration resistant prostate cancer.
All patients will be treated with stereotactic ablative radiotherapy and PSMA targeted radiopharmaceutical therapy with cessation of castration.
Half of patients are randomized to either receive, or not receive, subsequent testosterone replacement.

Who Can Enroll

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This clinical trial is for men with advanced prostate cancer that has spread to bones or other tissues and is no longer responding to standard hormone-blocking therapies.

Study Details

Start Date: December 14, 2023
Lead Sponsor: VA Office of Research and Development

Full Eligibility Criteria

Inclusion Criteria

Subject must be 18 years of age or older at the time the Informed Consent is signed
The subject (or legally acceptable representative if applicable) must provide written informed consent for the trial
Pathologic diagnosis of prostate cancer of adenocarcinoma histology; presence small cell/neuroendocrine carcinoma is exclusionary
Metastatic disease as documented by:
- Osseous metastases detected by technetium-99m (99mTc) planar bone scan or NaF PET scan, or CT scan at some point in patient's history
- Soft tissue metastases documented on CT or MRI
PSMA avid metastatic disease as determined by 18F-DCFPyL: at least one lesion with PSMA avidity greater than that of liver (see Prescribing Information for Pluvicto)
Progressive castration resistant prostate cancer as defined by serum testosterone 8.0 g/dL
- Absolute neutrophil count (ANC) > 1500/ µL
- Platelets > 75,000/ µL
- Total bilirubin 1.5 x ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 x ULN
- ALT and AST 3.0 x ULN ( 5 x ULN for participants with liver metastases) (Child-Pugh class A and B allowed; Child-Pugh class C is excluded)
- Creatinine 2.0 is allowed if EGFR >30 mL/min/1.73 m2)
Subject must agree to use contraception during the treatment period plus an additional 120 days after the last dose of study treatment and must refrain from donating sperm during this period

Exclusion Criteria

Visceral metastases including liver and brain (lung metastases are allowed)
Small cell/neuroendocrine carcinoma by hematoxylin and eosin light histology (immunohistochemical detection of rare/occasional cells that stain for neuroendocrine markers such as synaptophysin, neuron specific enolase, or chromogranin A is not sufficient to make a diagnosis of small cell/neuroendocrine carcinoma)
Anti-neoplastic therapies for prostate cancer must be completed > 2 weeks prior to Day 1 (initiation of first dose of PSMA RLT)
- Investigational agents must have been completed > 4 weeks of Day 1 Note: Participants must have recovered from all AEs due to previous therapies to Grade 1 or baseline
Participants with Grade 2 neuropathy may be eligible
- Herbal and non-herbal products that may decrease PSA levels other than medical castration and megestrol (up to 40 mg/day is allowed) for hot flashes
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention within 4 weeks prior to starting therapy
History of non-prostate active malignancy requiring treatment in the 24 months prior to Day 1 except for non-muscle invasive urothelial cancer, non-melanoma skin cancer, or any cancer that in the opinion of the investigator has been adequately treated and will not interfere with study procedures or interpretation of results
Active infection or conditions requiring treatment with antibiotics
Symptomatic local recurrence in the setting of prior curative intent therapy (surgery and/or radiation to the prostate)
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Subject is planning to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
Current or impending cord compression or another indication for urgent palliative radiation therapy