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

NCT06084338 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: SPLP-002-23M1I01CX002775
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

metastatic castration resistant prostate cancer; mCRPC; SBRT; Metastasis Directed Therapy; Lu177 PSMA; stereotactic body radiotherapy; stereotactic ablative radiotherapy; Pluvicto

Outcome Measures

Primary Outcomes (1)

• 6-month radiographic progression-free survival (rPFS)

  6-month radiographic progression-free survival (rPFS) measured by conventional imaging from date of initiation of PSMA radiopharmaceutical therapy

  6-months

Secondary Outcomes (10)

• safety as assessed by physician reported toxicity

  up to two years

• Patient reported health-related quality of life measured by Expanded Prostate Cancer Index Composite (EPIC-26)

  up to two years

• PSA30, PSA50, PSA90, maximal PSA response

  up to two years

• Time to PSA progression

  up to two years

• Objective response rate

  up to two years

Study Arms (2)

Arm 1

EXPERIMENTAL

Metastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration

Radiation: stereotactic ablative radiotherapy; Drug: Pluvicto

Arm 2

EXPERIMENTAL

Metastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration, followed by restoration of physiologic testosterone

Radiation: stereotactic ablative radiotherapy; Drug: Pluvicto; Drug: topical testosterone

Interventions

Pluvicto DRUG

PSMA targeted radiopharmaceutical therapy

Also known as: Lu177-PSMA

Arm 1; Arm 2

topical testosterone DRUG

Topical testosterone 1.62% gel

Also known as: androgel

Arm 2

stereotactic ablative radiotherapy RADIATION

Metastasis directed

Also known as: SBRT

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Patient must have or have had a prostate
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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
• 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
• metastases detectable on molecular imaging (PSMA and FDG PET) and amenable to SBRT
• % 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

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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (4)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073-1003, United States

RECRUITING

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-3030, United States

RECRUITING

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105-2303, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; Testosterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Nicholas George Nickols, MD PhD

  VA Greater Los Angeles Healthcare System, West Los Angeles, CA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas G Nickols, MD PhD

CONTACT

(310) 478-3711; nicholas.nickols@va.gov

Matthew B Rettig, MD

CONTACT

(310) 478-3711; matthew.rettig@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: October 16, 2023
• Study Start: December 14, 2023
• Primary Completion (Estimated): November 29, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)