STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer (STARLiT)

STARLiT: STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer: A Phase I/II Trial

The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer.

Participants will receive one dose of Pluvicto, followed by radiation about 6 weeks later. Radiation therapy will be completed in 5 treatments over the period of 2 weeks. A second dose of Pluvicto will be given 6 weeks after radiation is complete. Some participants may also receive a third dose of Pluvicto, and this would be given 6 weeks after the second dose of Pluvicto.

Study Overview

• Status: Recruiting
• Conditions: Malignant Neoplasm of Prostate; Locally Advanced Prostate Cancer
• Intervention / Treatment: Drug: Lu-PSMA-617; Radiation: 5-fraction Stereotactic Body Radiation Therapy (SBRT)

Detailed Description

Prostate cancer is the most common cancer in men worldwide and second leading cause of cancer death in men. The most common treatment for prostate cancer is radiation therapy (RT) plus long-term androgen deprivation therapy (ADT) for 18-36 months with a consideration for the addition of abiraterone acetate.

With the introduction of abiraterone and other second generation androgen signaling inhibitors (ARSIs) there is great interest in shortening the duration of systemic therapy. This interest stems from the high toxicity rates of ADT and substantial impact on patient-reported quality of life (QoL). The use of ADT is associated with some adverse events. Therefore, the combination of adverse event risks and decrease in quality of life associated with castration have resulted in decreased compliance to long term ADT and even ARSIs, where approximately 50% of patients with locally advanced disease either decline any ADT or stop treatment early. The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer.

This clinical trial will evaluate the safety of using Lu-PSMA-617 with SBRT to the prostate and pelvic lymph nodes, and to determine whether Lu-PSMA-617 can replace androgen deprivation therapy (ADT) to improve oncologic outcomes by use of cytotoxic agents, avoid ADT related side effects, and improve compliance for participants to receive systemic therapy.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Angela Y Jia, MD, PhD; Phone Number: 216-844-3262; Email: Angela.Jia@UHhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be ≥ 18 years of age.
• ECOG performance status ≤ 1
• Histologic confirmation of prostate adenocarcinoma of the prostate

• PSMA avid disease on PSMA PET/CT, where the tumor in the prostate has SUVmax ≥ 10.

  • PSMA PET/CT must be obtained within 4 months.

• Need ≥ 1 criteria:

  • Node positive disease on PSMA PET/CT or conventional imaging, as defined by having any of the following:

    • Pelvic nodal disease (cN1) as defined by LN stations that commence at the bifurcation of the common iliac vessels
    • Regional nodal disease (M1a) as defined by LN stations that commence at the bifurcation of the aorta and bifurcation of the proximal inferior vena cava to the common iliac veins.

  • In the absence of nodal metastasis, must have ≥ 2 of the following

    • i. cT3a or cT3b by conventional imaging (MRI) or PSMA PET/CT
    • ii. Grade group ≥ 4
    • iii. PSA ≥ 40 ng/mL

• Adequate organ and marrow function to receive treatment:

  • Hemoglobin > 10 g/dL
  • White blood cell (WBC) > 3000 / mL
  • Absolute neutrophil count ≥ 1,500 / mcL
  • Platelets ≥ 100,000 / mcL
  • Creatinine ≤ 1.5x ULN
  • Estimated glomerular filtration rate (eGFR)* > 50 mL/min
  • Total bilirubin** < 2× ULN
  • Albumin > 3 g/dL

  • Aspartate aminotransferase (AST) < 3× ULN

    • *based upon Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Participants with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only participants with non-obstructive pathology will be included in the study.
    • ** Total bilirubin ≤ 2x ULN (except for participants with known Gilbert's Syndrome ≤ 3x ULN is permitted)
• International Prostate Symptoms Score (IPSS) ≤ 15.
• Medically fit for treatment and agreeable to follow-up.
• Ability to understand and the willingness to sign a written informed consent.
• Participants with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 14 weeks from receiving the last dose of Lu-PSMA-617. Participants must also not donate sperm for 14 weeks from receiving the last dose of Lu-PSMA-617.

Exclusion Criteria:

• Clinical or radiographic evidence of distant metastatic disease (M1a above aortic bifurcation, M1b, or M1c) by any imaging. Participants are allowed to M1a nodal disease that is below the aortic bifurcation. Negative PSMA PET/CT is an acceptable substitute to conventional staging.
• Prostate gland size >90 cc measured by CT, ultrasound, or MRI
• Prior head and neck radiation therapy.
• Prior treatment for prostate cancer (incudes chemotherapy, radiation therapy, or anti-androgen therapy).
• Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
• Prohibited 3 months before participant registration and during administration of study treatment: oral ketoconazole, , estrogens, and radiopharmaceuticals.
• History of prior pelvic radiation therapy.
• Enrollment concurrently in another investigational drug study within 6 months of registration.
• History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer.
• History of prior myelodysplastic syndrome or acute leukemia.
• History of or active Crohn's disease or ulcerative colitis.
• Contraindication to or inability to tolerate PSMA/PET.
• Any condition that in the opinion of the investigator would preclude participation in this study.
• Inability to adhere to radiation safety measures in hospital or at home
• Prior treatment with radionuclide therapies, 177Lu-PSMA-617 or other
• Reduced salivary gland function with baseline CTCAE Gr > 1 dry mouth will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lu-PSMA-617 + SBRT; Lu-PSMA-617: 7.4GBq intravenous infusion once with cycle 1, followed by 7.4GBq cycle 2 that is delivered 6 weeks after SBRT , and potentially 7.4GBq cycle #3 delivered 6 weeks after cycle #2 pending dose escalation; Radiation therapy: 5 fractions to prostate and elective nodal irradiation, SBRT, delivered 6 weeks after cycle 1 of 177Lu-PSMA-617

Drug: Lu-PSMA-617; Lu-PSMA will be administered at a fixed dose of 7.4GBq per cycle, on a dose escalation schedule: Level 0: Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT.; Level 1 (Starting Dose Level): Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT, followed 6 weeks later by cycle 2.; Level 2: Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT, followed 6 weeks later by cycle 2, followed 6 weeks later by cycle 3.; Other Names: Pluvicto; Radiation: 5-fraction Stereotactic Body Radiation Therapy (SBRT); Prostate and nodal SBRT will begin at the completion of cycle 1 (6 weeks after the first Lu-PSMA-617 infusion, ± 4 weeks).; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Maximum tolerated dose (MTD) of Lu-PSMA-617	The Phase I goal is to determine the maximally tolerated dose (MTD) of Lu-PSMA-617 when administered with prostate SBRT treatment. The MTD will be captured by analyzing the incidence of dose limiting toxicities occurring within the four weeks after the last dose of treatment.	4 weeks after final dose of treatment (treatment expected to last up to six months)
Phase II: Androgen deprivation therapy (ADT)-free survival	The Phase II goal is to determine the 3-year rate of ADT-free survival.	3 years post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Progression Free Survival	PSA progression-free survival will be analyzed at 24 months post last dose of treatment.	2 years post treatment
Overall Survival (OS)	Overall Survival (OS) is defined as the time from Day 1 until death due to any cause. For subjects who do not die, time to death will be censored at the time of last contact.	5 years post treatment
Prostate Cancer-specific Survival (PCSM)	Prostate cancer specific mortality (PCSM) is defined the time from Day 1 to death directly attributable to prostate cancer, death from treatment complications, or death from unknown causes in participants with active prostate cancer or previously documented clinical or biochemical relapse.	5 years post treatment
Cumulative incidence of distant metastases	Distant metastases (DM) is defined as the time from Day 1 until development of distant metastases on CT, MRI, bone scan or PSMA PET, or death from prostate cancer.	5 years post treatment
Time to any salvage therapy	The time to any salvage therapy, or Time-to-next-intervention (TTNI), is defined as is defined as the time from Day 1 to the time of initiation of any additional (i.e., outside of planned protocol treatment) cancer-directed therapy, including but not limited to androgen deprivation, other systemic prostate cancer therapeutics, palliative radiotherapy, or surgical intervention specifically addressing complications of metastases. In the absence of a defining event, TTNI will be censored at the date of last visit documenting absence of interventions.	5 years post treatment
Change in Quality of life score as measured by EPIC-26	EPIC-26 is a short form version of the full Expanded Prostate Cancer Index Composite (EPIC). This version contains 26 items and the same 5 domains as the full version of EPIC: urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Response options for each EPIC item for a Likert scale, and multi-item scare scores are transported linearly to a 0-100 scale with higher scores representing better QoL. The time frame asked in the question relates to symptoms experienced within the prior 4 weeks.	Baseline to 5 years post treatment
Change in Quality of life score as measured by XeQoLS	Xerostomia-related Quality of Life Questionnaire (XeQoLS) is a questionnaire used to measure how dry mouth and salivary dysfunction affect participants' quality of life (QoL). This questionnaire consists of 15 questions across four major domains: physical functioning, personal/psychological functioning, social functioning, and pain/discomfort issues. The XeQoLS is a self-administered tool, and participants are asked to rate each symptom on a 5-point Likert scale from 0 to 4, with higher scores indicating increased xerostomia burden. An average of scores in each domain is calculated, and the average score ranges from 0 to 4. A total score is calculated as an average of the scores from each of the domain.	Baseline to 5 years post treatment
Change in Quality of life score as measured by FACT-RNT	FACT-RNT is a patient-reported outcomes (PRO) measure for PCa participants receiving radionuclide therapy. It has not yet been validated in a prospective manner. It consists of 15 questions on a 5-point Likert scale, in a recall period of the past 7 days. Each item score is added, and the sum is linearly transformed to produce the final summary score ranging from 0 to 100, with higher scores representing better QoL.	Baseline to 5 years post treatment
Time-to-castration-resistant prostate cancer	To determine the average time-to-castration-resistant prostate cancer.	5 years post treatment
Rate of participants with post treatment PSA in goal range	Rate of obtaining a post-treatment PSA of ≤ 0.5 ng/mL following treatment with 177Lu-PSMA-617 and prostate and nodal SBRT.	12 weeks post treatment
Incidence of acute toxicity	The goal is to describe acute toxicity following treatment with Lu-PSMA-617 and prostate and nodal SBRT.	5 years post treatment
Incidence of late toxicity	The goal is to describe late treatment toxicity following treatment with Lu-PSMA-617 and prostate and nodal SBRT.	5 years post treatment
Biochemical recurrence (BCR)	To determine the rate of biochemical recurrence (BCR), defined as PSA nadir + 2 ng/mL.	5 years post treatment
Proportion of participants with PSA50-RR	The proportion of participants with PSA50-RR at 12 weeks post all treatment will be summarized with 95% confidence interval (CI), where PSA50-RR is defined as the proportion of men with a PSA reduction of at least 50% at 6 weeks after the last 177Lu-PSMA-617 treatment, compared with baseline PSA prior to 177Lu-PSMA-617 treatment.	12 weeks post treatment

Collaborators and Investigators

• Sponsor: Angela Y. Jia, MD PhD
• Investigators: Principal Investigator: Angela Y Jia, MD, PhD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center; Study Chair: Daniel E Spratt, MD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prostate cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Pluvicto
• Other Study ID Numbers: CASE7824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlies publication
• IPD Sharing Time Frame: Compiled and analyzed participant data will be published upon study completion. Publisher may request Protocol and Statistical Analysis Plan.
• IPD Sharing Access Criteria: To be shared with investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No