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Prostate CancerPhase 2NCT06084338

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

A Phase 2 study testing stereotactic ablative radiotherapy, Pluvicto and topical testosterone in people with Prostate Cancer, run by VA Office of Research and Development at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men onlyHealthy volunteers can take part
Conditions the study is for
Prostate Cancer
What is being tested?
stereotactic ablative radiotherapy, Pluvicto and topical testosterone
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
4 sitesUnited States
Study dates
14 Dec 2023to 31 Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

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

United States4 sites, 4 recruiting

  • VA Ann Arbor Healthcare System, Ann Arbor, MI

    Ann Arbor, Michigan, 48105-2303

    David Elliott, MD, david.elliott1@va.gov

    Recruiting

  • Edward Hines Jr. VA Hospital, Hines, IL

    Hines, Illinois, 60141-3030

    Abhishek Solanki, MD, abhishek.solanki@va.gov

    Recruiting

  • Richard L. Roudebush VA Medical Center, Indianapolis, IN

    Indianapolis, Indiana, 46202-2884

    Ronald Shapiro, MD, ronald.shapiro@va.gov

    Recruiting

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

    West Los Angeles, California, 90073-1003

    Nicholas G Nickols, MD PhD, (310) 478-3711, nicholas.nickols@va.gov

    Matthew B Rettig, MD, (310) 478-3711, matthew.rettig@va.gov

    Recruiting

Other trials in United States

About this study

Official title: Phase II Trial of Targeted Radiation With no Castration for Mcrpc

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.

Read the detailed description

This is a randomized, parallel-arm, two-stage open-label phase 2 study of comprehensive metastasis directed therapy in the form of stereotactic body radiation therapy (SBRT) to all detectable sites of disease plus PSMA targeted radiopharmaceutical therapy (pluvicto), discontinuation of castration, with and without testosterone replacement therapy (TRT) in metastatic castration resistant prostate cancer (mCRPC).

Conditions
Prostate Cancer
Being tested
stereotactic ablative radiotherapy, Pluvicto, topical testosterone
Keywords
metastatic castration resistant prostate cancer, mCRPC, SBRT, Metastasis Directed Therapy, Lu177 PSMA, stereotactic body radiotherapy, stereotactic ablative radiotherapy, Pluvicto
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • stereotactic ablative radiotherapyRadiation

    Also called SBRT

    Metastasis directed

  • PluvictoDrug

    Also called Lu177-PSMA

    PSMA targeted radiopharmaceutical therapy

  • topical testosteroneDrug

    Also called androgel

    Topical testosterone 1.62% gel

Study groups in NCT06084338
Study groupRoleWhat they receive
Arm 1ExperimentalMetastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration
Receives: Radiation: stereotactic ablative radiotherapy; Drug: Pluvicto
Arm 2ExperimentalMetastasis 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
Receives: Radiation: stereotactic ablative radiotherapy; Drug: Pluvicto; Drug: topical testosterone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6-months

Secondary outcomes (10)

  1. safety as assessed by physician reported toxicity

    Physician reported Common Terminology Criteria for Adverse Events (CTCAE version 5.0)

    Measured: up to two years

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

    EPIC-26 contains 26 items in 5 domains (Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal). Raw scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.

    Measured: up to two years

  3. PSA30, PSA50, PSA90, maximal PSA response

    This is the rate of PSA response (PSA decrease by 30%, 50%, 90%), and maximal response

    Measured: up to two years

  4. Time to PSA progression

    Time to PSA progression per PCWG3 criteria, from date of initiation of PSMA radiopharmaceutical therapy

    Measured: up to two years

  5. Objective response rate

    Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) from date of initiation of PSMA radiopharmaceutical therapy

    Measured: up to two years

  6. Time to radiographic progression

    Time-to-event, Bone progression by Prostate Cancer Working Group 3 (PCWG3) criteria and/or soft tissue progression by RECIST v1.1, from date of initiation of PSMA radiopharmaceutical therapy

    Measured: up to two years

  7. PSMA PET response

    Measured using Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE)

    Measured: up to two years

  8. Progression Free Survival

    Time-to-event, a composite between time to PSA progression (PCWG3) and/or radiographic progression (PCWG3 for bone, RECIST 1.1 for soft tissue), from date of initiation of PSMA radiopharmaceutical therapy

    Measured: up to two years

  9. Overall survival

    Time-to-event, from date of initiation of PSMA radiopharmaceutical therapy

    Measured: up to two years

  10. Patient reported health-related quality of life measured by The Functional Assessment of Cancer Therapy-Prostate (FACT-P).

    FACT-P includes a general functional status scale (consisting of four subscales: physical wellbeing, social and family wellbeing, emotional wellbeing, and functional wellbeing) and a prostate-cancer-specific subscale. Total score is calculated with general function and prostate-cancer-specific scores, and ranges from 0 to 156 (higher scores indicate better functional status).

    Measured: up to two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2023
  2. Study start14 Dec 2023
  3. Primary completion29 Nov 2027 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06084338
Sponsor's protocol ID
SPLP-002-23M
Other IDs
1I01CX002775
Status last verified
Dec 2025
First submitted
10 Oct 2023
Last updated
31 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing stereotactic ablative radiotherapy, Pluvicto and topical testosterone in people with Prostate Cancer, run by VA Office of Research and Development at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nicholas G Nickols, MD PhD ((310) 478-3711, nicholas.nickols@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month radiographic progression-free survival (rPFS) (time frame: 6-months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06084338.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.

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