Lu-PSMA and Stereotactic Radiotherapy Versus Radiotherapy Alone for Prostate Cancer (LUST)

NCT05893381 | Recruiting Phase 2

• 1 other identifier: IRST185.09
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

Multicenter, open-label, parallel-group, phase II randomized study in patients with oligometastatic prostate cancer with 1-3 asymptomatic metastases of the soft tissue or bone. Eligible patients will be randomized at 1:1 ratio to Stereotactic Radiotherapy followed by Lu-PSMA (arm A) or Stereotactic Radiotherapy (arm B)

Conditions

Prostate Cancer

Keywords

PSMA PET/CT positive

Outcome Measures

Primary Outcomes (1)

• 12-month PSA (Prostate-Specific Antigen)-progression-free survival (PSA-PFS)

  To determine the proportion of men with oligometastatic hormone sensitive prostate cancer who have PSA progressed after 12 months from randomization to Stereotactic Radiotherapy and Lu-PSMA versus Radiotherapy alone.

  12-months

Secondary Outcomes (5)

• 12-month radiographic Progression-free survival (rPFS), Androgen Deprivation Therapy-Free survival (ADT-FS) and Total progression-free survival (PSA-PFS+rPFS)

  12-months

• Incidence of Treatment-Emergent Adverse Events [Toxicity]

  60 months

• Overall survival (OS)

  60 months

• Proportion of subjects with undetectable PSA (<0.2 ng/mL)

  60 months

• Quality of life questionnaire (QLQ)

  60 months

Study Arms (2)

Stereotactic Radiotherapy followed by Lu-PSMA (arm A)

EXPERIMENTAL

Ablative stereotactic radiation on the metastatic sites. Delivered in a 1 to 5 fractions regimen. 177Lu-PSMA-I\&T in 2 cycles of treatment at 6-8 weekly intervals at a dosage of 7.4 Gigabequerel (GBq)

Drug: [177Lu]Lu-PSMA I&T; Radiation: Stereotactic Radiotherapy

Stereotactic Radiotherapy (arm B)

ACTIVE COMPARATOR

Ablative stereotactic radiation on the metastatic sites. Delivered in a 1 to 5 fractions regimen.

Radiation: Stereotactic Radiotherapy

Interventions

[177Lu]Lu-PSMA I&T DRUG

The radiopharmaceutical 177Lu-PSMA-I\&T will be administered, by slow intravenous injection, in 2 cycles of treatment at 6-8 weekly intervals at a dosage of 7.4 GBq.

Also known as: 177Lu-PSMA

Stereotactic Radiotherapy followed by Lu-PSMA (arm A)

Stereotactic Radiotherapy RADIATION

Ablative stereotactic radiation on the metastatic sites. Delivered in a 1 to 5 fractions regimen, depending on the target size and the surrounding normal tissue constraints,

Also known as: Ablative stereotactic radiation

Stereotactic Radiotherapy (arm B); Stereotactic Radiotherapy followed by Lu-PSMA (arm A)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with prostate cancer must have 1-3 asymptomatic metastatic lesions that are ≤ 5.0 cm or \< 250 cm3 documented at CT/MRI or WBD-MRI.
• PSMA-PET/CT positive scan matching with lesions documented on baseline CT/MRI or WBD-MRI.
• Patients must have had their primary tumor treated with surgery and/or radiation and previous salvage radiation to the prostate bed or pelvis is allowed.
• Patients will be admitted to the therapeutic phase only if diagnostic PET/CT PSMA SUV max is ≥ 3.
• Histologic confirmation of malignancy (primary or metastatic tumor).
• Prostate specific antigen (PSA) ≥ 0.2 ng/mL but ≤ 50 ng/mL and Testosterone ≥ 125 ng/dL.
• PSA doubling time (PSADT) \< 15 months. PSADT will be calculated using as many PSA values that are available from time of relapse (PSA \> 0.2 ng/dL).
• Patients unfit or refusing ADT.
• Patients may have had prior systemic therapy and/or ADT associated with treatment of their primary prostate cancer. Patients may have had ADT associated with salvage radiation therapy.
• Patients must be ≥ 18 years of age.
• Patient understands the purpose of the study and the procedures required for it; the patient is willing to participate in the study and to sign a written informed consent document.
• Patients must have an Eastern Cooperative Oncology Group performance status ≤ 2.
• Patients should have a life expectancy of at least 6 months.
• Patients must have normal organ and marrow function as defined as:
• Leukocytes \>2,000/μL;

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• No more than 3 years of ADT is allowed, with the most recent ADT treatment having occurred more than 6 months prior to enrollment.
• PSMA -PET/CT scan more than 3 months.
• Spinal cord compression or impending spinal cord compression.
• Suspected pulmonary and/or liver metastases.
• Bone metastasis in a femoral bone.
• Previous radiation therapy on the metastatic site.
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. A window of 3 days is permitted.
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening. A window of 3 days is permitted.
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177-Lu-PSMA- I \& T or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Unable to lie flat during or tolerable SABR.
• Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma);

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (2)

UO Medicina Nucleare, AUSL della Romagna

Cesena, FC, 47521, Italy

RECRUITING

UO Medicina Nucleare, IRCCS IRST

Meldola, FC, 47014, Italy

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiosurgery

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Federica Matteucci

  UO Medicina Nucleare, IRCCS IRST

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oriana Nanni

CONTACT

+390543739100; cc.ubsc@irst.emr.it

Bernadette Vertogen

CONTACT

+390544286058; cc.ubsc@irst.emr.it

Study Design

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

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: June 7, 2023
• Study Start: June 27, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): April 1, 2032
• Last Updated: December 3, 2025

Record last verified: 2024-12

Locations

IT (2)