Clinical trial NCT05496959: 177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study
Official title: 177-Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (Lunar)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Oligometastatic Prostate Carcinoma
Prostate Adenocarcinoma
Recurrent Prostate Adenocarcinoma
Stage IVB Prostate Cancer AJCC v8
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2022-08-11
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT)-based progression-free survival (PFS)
timeFrame: 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:
measure: Disease progression
timeFrame: At 24 months
measure: PSA-based progression
timeFrame: Up to 24 months
measure: Incidence of adverse events (AEs)
timeFrame: Up to 60 months
measure: Patient-reported quality of life as reported by the Brief Pain Inventory form
timeFrame: Baseline up to 1 year
measure: Androgen deprivation therapy-free survival (ADT-FS)
timeFrame: Time from starting treatment to the time of initiation of palliative ADT, assessed up to 60 months
measure: Time to progression
timeFrame: Time from completing SBRT to the time of first documented tumor progression or new lesions by PSMA PET/CT or initiation of ADT, assessed up to 60 months
measure: Time to local progression (TTLP)
timeFrame: Time from completing SBRT to identification of progression of treated lesions, assessed up to 60 months
measure: Time to new metastasis (TNM)
timeFrame: Time from completing SBRT to the time of a new documented tumor metastasis by PSMA PET/CT, assessed up to 24 months
measure: Overall survival (OS)
timeFrame: Time from starting treatment until death due to any cause, assessed up to 60 months
measure: Local control (LC)
timeFrame: Time from starting treatment until local relapse is documented by PSMA PET/CT based criteria, assessed up to 24 months
measure: Regional control (RC)
timeFrame: Time from starting treatment until regional relapse is documented by PSMA PET/CT based criteria, assessed up to 24 months
measure: Duration of complete response (CR) or partial response (PR)
timeFrame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that current or progressive disease is objectively documented, assessed up to 60 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA / Jonsson Comprehensive Cancer Center
state: California
Study officials:
affiliation: UCLA / Jonsson Comprehensive Cancer Center
name: Amar Kishan, MD
role: PRINCIPAL_INVESTIGATOR
References: