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

Recruiting now · Phase 2

Conditions studied: Prostate Cancer

In brief

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.

Key facts

Study ID: NCT06084338
Run by: VA Office of Research and Development
People needed: 60
Starts: 2023-12-14
Expected to finish: 2028-12-31
Last updated by the study team: 2025-12-31

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: accepted.

You may qualify if…

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 < 50 ng/mL and one of the following:
PSA progression confirmed per Prostate Cancer Clinical Trials Working Group (PCWG3)
Radiographic progression of soft tissues according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) modified based on PCWG3, or radiographic progression of bone according to PCWG3
Prior use of a novel AR signaling inhibitor for 4 weeks, including abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and/or darolutamide
NOTE: These AR signaling inhibitors may have been used for mCSPC, M0CRPC, and/or mCRPC.
ECOG PS grade of 0-2
10 metastases detectable on molecular imaging (PSMA and FDG PET) and amenable to SBRT
20% of metastases that are FDG avid but PSMA negative
Metastases that are not detectable on PSMA and FDG PET do not count toward the total number of metastases, as they are presumed to represent adequately treated sites of disease
Life expectancy 6 months
Adequate organ function:
Hemoglobin (hgb) > 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 mg/dL) during screening evaluation (>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

You may not qualify if…

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

Where it is running

VA Greater Los Angeles Healthcare System, West Los Angeles, CA — West Los Angeles, California, United States (enrolling)
Edward Hines Jr. VA Hospital, Hines, IL — Hines, Illinois, United States (enrolling)
Richard L. Roudebush VA Medical Center, Indianapolis, IN — Indianapolis, Indiana, United States (enrolling)
VA Ann Arbor Healthcare System, Ann Arbor, MI — Ann Arbor, Michigan, United States (enrolling)

Full record on ClinicalTrials.gov

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