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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.

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.

Lutetium Lu-177 PNT2002

Quality-of-Life Assessment

Stereotactic Body Radiation Therapy

Amar Kishan, MD

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.

PRIMARY OBJECTIVE:

I. To assess progression-free survival for men with oligorecurrent prostate cancer after stereotactic body radiotherapy (SBRT) versus SBRT plus neoadjuvant lutetium Lu-177 PNT2002 (177Lu-PNT2002), with progression defined on the basis of prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT) scans obtained at standard intervals (12 months and 24 months post-SBRT) or at the time of prostate-specific antigen (PSA)-based biochemical progression, or initiation of salvage therapy or death.

SECONDARY OBJECTIVES:

I. To evaluate disease burden of disease (including local control of irradiated lesions and presence of other disease) on a PSMA PET/CT obtained 24 months after SBRT of SBRT versus SBRT + 177Lu-PNT2002 in patients with oligometastatic disease who have not progressed by that point.

II. To assess physician-scored toxicity (Common Terminology Criteria for Adverse Events version 5.0 \[CTCAE v 5.0\]) of SBRT versus SBRT + 177Lu-PNT2002 in patients with oligometastatic disease.

III. To assess patient-reported quality of life (based on the brief pain inventory scale) after SBRT versus SBRT + 177Lu-PNT2002 in patients with oligometastatic disease.

IV. To assess androgen deprivation therapy (ADT)-free survival after SBRT versus SBRT + 177Lu-PNT2002 in patients with oligometastatic disease.

V. To determine local control of irradiated lesion at 12 months after SBRT versus SBRT + 177Lu-PNT2002 in patients with oligometastatic disease (based on a scheduled PSMA-PET).

VI. To assess time to locoregional progression, time to distant progression, time to new metastasis, and duration of response after SBRT versus SBRT + 177Lu-PNT2002 in patients with oligometastatic disease (based on standard of care imaging).

CORRELATIVE OBJECTIVES:

I. To enumerate circulating tumor cells (CTCs) and circulating tumor deoxyribonucleic acid (ctDNA) at baseline, 3 months, 6 months, and 12 months after SBRT.

II. To quantitatively sequence T-cell receptor (TCR) repertoires using peripheral blood monocytes at baseline, 3 months, 6 months, and 12 months after SBRT.

III. To perform radiomics analysis on PSMA PET/CT scans performed at +12 months (mo.), +24 months post-SBRT, or at time of progression.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: 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.

ARM 2: Patients receive 177Lu-PNT2002 intravenously (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.

After completion of study treatment patients are followed up at 1, 3, 6, 9, and 12 months, then every 6 months until 60 months of total follow-up.

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

177-Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (Lunar)

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.

Progression as based PSMA PET/CT scan (with progression). Will be analyzed descriptively.

Defined as follows: (a) For pre-enrollment PSA \< 0.5 ng/mL, PSA-based progression defined as 0.2 ng/mL increase and (b) For pre-enrollment PSA \>= 0.5 ng/mL, PSA-based progression defined as 50% increase over pre-treatment value.

Acute and late physician-scored toxicity Common Terminology Criteria for Adverse Events (CTCAE version 5.0 scale). AEs will be summarized by type and grade. All patients who receive at least one fraction of SBRT in the control arm will be evaluable for toxicity from the time of their first treatment from SBRT; all patients who receive 177Lu-PNT2002 in the experimental arm will be evaluable for toxicity from the time of their first treatment with 177Lu-PNT2002.

Quality of life following SBRT versus 177Lu-PNT2002 +SBRT will be evaluated based on responses to the Brief Pain Inventory form, which will be tabulated at baseline and each follow-up visit (3 months, 6 months, 9 months and 1 year).

The Brief Pain Inventory is a self-administered 9-item questionnaire, tabular scored from 0 - 130 with lower scores indicating a better outcome.

The KM method will be used to summarize ADT-FS.

The KM method will be used to summarize TTLP.

The KM method will be used to summarize TNM.

The KM method will be used to summarize OS.

The KM method will be used to summarize LC.

failure in an adjacent lymph node region (for nodal targets) detected by PSMA PET/CT

The KM method will be used to summarize the duration of complete or partial response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study	NCT05496959	Oligometastatic... Prostate Adenoc... Recurrent Prost... Stage IVB Prost...	Lutetium Lu-177... Quality-of-Life... Stereotactic Bo...	18 Years -	Jonsson Comprehensive Cancer Center
177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study	NCT05496959	Oligometastatic... Prostate Adenoc... Recurrent Prost... Stage IVB Prost...	Lutetium Lu-177... Quality-of-Life... Stereotactic Bo...	18 Years -	Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for recurrent prostate adenocarcinoma