177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study

NCT05496959 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 22-000750NCI-2022-05748
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests whether 177-Lutetium-PSMA given before stereotactic body radiotherapy (SBRT) works to improve cancer control rate in patients with 1-5 prostate cancer tumors that have come back after prior treatment (oligorecurrent). Radioactive drugs, such as 177-Lutetium-PSMA, may carry radiation directly to tumor cells and not harm normal cells. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving 177-Lutetium-PSMA before SBRT may make the SBRT more effective.

Conditions

Oligometastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Adenocarcinoma; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT)-based progression-free survival (PFS)

  Will compare PSMA PET/CT-based PFS for patients with oligoprogressive prostate cancer treated with SBRT to all known sites of disease on PSMA PET/CT versus patients treated with 177Lu-PNT2002 prior to SBRT to all known sites of disease. PSMA PET/CT-based progression is defined as either (a) a new lesion on PSMA PET/CT with or without a serum prostate-specific antigen (PSA) increase or (b) local progression on PSMA (\> 30% increase in lesion standard uptake value \[SUV\] or increase of \> 20% in the sum of the longest diameter of all target lesions), regardless of new lesions, and a serum PSA increase. A serum PSA increase for the purposes of this definition will be based on the definition of PSA-based progression. The Kaplan-Meier (KM) method will be used to summarize PFS and log-rank test will be used to compare PFS between the two arms.

  Time from the date of stereotactic body radiotherapy (SBRT) completion to the date of disease progression or death, whichever happens earlier, assessed up to 24 months

Secondary Outcomes (12)

• Disease progression

  At 24 months

• PSA-based progression

  Up to 24 months

• Incidence of adverse events (AEs)

  Up to 60 months

• Patient-reported quality of life as reported by the Brief Pain Inventory form

  Baseline up to 1 year

• Androgen deprivation therapy-free survival (ADT-FS)

  Time from starting treatment to the time of initiation of palliative ADT, assessed up to 60 months

Study Arms (2)

Arm 1 (SBRT)

ACTIVE COMPARATOR

Beginning on day 1, patients undergo SBRT to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity.

Other: Quality-of-Life Assessment; Radiation: Stereotactic Body Radiation Therapy

Arm 2 (177Lu-PNT2002, SBRT)

EXPERIMENTAL

Patients receive 177Lu-PNT2002 IV over 1-10 minutes on days -112 and -56 in the absence of disease progression or unacceptable toxicity. Beginning on day 1, patients then undergo SBRT to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity.

Drug: Lutetium Lu-177 PNT2002; Other: Quality-of-Life Assessment; Radiation: Stereotactic Body Radiation Therapy

Interventions

Lutetium Lu-177 PNT2002 DRUG

Given IV

Also known as: 177Lu-labeled PNT2002, 177Lu-PNT2002, [Lu-177]-PNT2002, [Lu-177]-PSMA-I and T, Lu177-PNT2002, Lutetium Lu-177-PNT2002

Arm 2 (177Lu-PNT2002, SBRT)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm 1 (SBRT); Arm 2 (177Lu-PNT2002, SBRT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Arm 1 (SBRT); Arm 2 (177Lu-PNT2002, SBRT)

Eligibility Criteria

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

You may qualify if:

• Oligorecurrent prostate cancer as determined by the presence of 1-5 asymptomatic lesions outside the prostate or prostate bed identified on PSMA PET/CT by local readers
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• No indication for urgent or emergent radiation
• Histologic confirmation of prostate adenocarcinoma (histology from original treatment acceptable)
• White blood cell count \>= 2.5 × 10\^9/L
• Platelets \>= 100 × 10\^9/L
• Hemoglobin \>= 9 g/dL
• Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN); or up to 3 × ULN if known history of Gilbert's syndrome
• Alanine aminotransferase or aspartate aminotransferase =\< 3.0 × ULN or =\< 5.0 × ULN for patients with liver metastases
• Serum creatinine =\< 1.5 × ULN or creatinine clearance \>= 50 mL/min
• Serum albumin \> 3.0 g/dL
• Partner and patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration
• Ability to understand, and willingness to sign, the written informed consent

You may not qualify if:

• Patients with neuroendocrine or small cell carcinoma of the prostate
• Patients with castrate-resistant disease (i.e., PSA \> 0.5 ng/mL with serum testosterone \< 150 ng/dL)
• Patients who received androgen deprivation therapy within 6 months of trial enrollment
• Concurrent systemic therapy for a solid organ malignancy
• Spinal cord compression
• Inability to lie flat
• Known hypersensitivity to components of 177Lu-PNT2002
• Serum creatinine \> 1.5 × ULN or creatinine clearance \< 50 mL/min
• Total bilirubin \> 1.5 × ULN or \> 3.0 × ULN if known history of Gilbert's syndrome
• Alanine aminotransferase or aspartate aminotransferase \> 3 × ULN (or 5 × ULN for patients with known liver metastases)
• De novo oligometastatic disease

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Kishan AU, Valle LF, Wilhalme H, Felix C, Nabong R, Juarez-Casillas JE, Flores K, Ma TM, Ludwig V, Nakayama M, Ells Z, Dahlbom M, Lauria M, Meyer C, Cao M, Weidhaas JB, Telesca D, McGreevy K, Nickols NG, Karasik D, Parmisano S, Basehart TV, Brisbane W, Marks L, Rettig MB, Reiter RE, Boutros PC, Allen-Auerbach M, Czernin J, Steinberg ML, Calais J. 177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study. J Clin Oncol. 2025 Dec 20;43(36):3812-3821. doi: 10.1200/JCO-25-01553. Epub 2025 Nov 12.

  PMID: 41223345 DERIVED

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

• Amar Kishan, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

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: August 8, 2022
• First Posted: August 11, 2022
• Study Start: September 2, 2022
• Primary Completion (Estimated): September 1, 2032
• Study Completion (Estimated): September 1, 2033
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

US (1)