Targeted radiation therapy for advanced prostate cancer without castration

Phase II Trial of Targeted Radiation With no Castration for Mcrpc

This study is testing a new combination of targeted radiation treatments for men with advanced prostate cancer to see if it helps them do better without the need for hormone therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: VA Office of Research and Development (fed)
• Drugs / interventions: radiation, prednisone
• Locations: 4 sites (West Los Angeles, California and 3 other locations)
• Trial ID: NCT06084338 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness of a combination treatment for metastatic castration resistant prostate cancer (mCRPC) using stereotactic ablative radiotherapy and PSMA targeted radiopharmaceutical therapy, while discontinuing castration. Patients will be randomized to receive or not receive testosterone replacement therapy after the initial treatment. The study aims to determine if this approach can improve outcomes for patients with mCRPC. It is a phase 2, open-label trial involving multiple VA healthcare systems.

Who should consider this trial

Good fit: Ideal candidates include adult males aged 18 and older with metastatic castration resistant prostate cancer and documented PSMA avid disease.

Not a fit: Patients with small cell or neuroendocrine carcinoma, or those without detectable metastatic disease, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for managing advanced prostate cancer without the need for ongoing castration.

How similar studies have performed: While this approach combines established therapies, the specific combination and cessation of castration is novel and has not been extensively tested in prior studies.

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 \< 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

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

Where this trial is running

West Los Angeles, California and 3 other locations

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

Study contacts

• Principal investigator: Nicholas George Nickols, MD PhD — VA Greater Los Angeles Healthcare System, West Los Angeles, CA
• Study coordinator: Nicholas G Nickols, MD PhD

Conditions: Prostate Cancer, metastatic castration resistant prostate cancer, mCRPC, SBRT, Metastasis Directed Therapy, Lu177 PSMA, stereotactic body radiotherapy, stereotactic ablative radiotherapy