Clinical trial NCT06105918: Radioligand Therapy After PSMA PET Guided External Beam Radiotherapy for Treating Post-Prostatectomy Patients with Biochemically Recurrent Prostate Cancer
Official title: Phase 1 Trial to Determine Safety and Feasibility in Treating Biochemical Recurrence Post-Prostatectomy with PSMA PET Guided External Beam Radiotherapy Followed by Consolidative Radioligand Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Biochemically Recurrent Prostate Carcinoma
Prostate Adenocarcinoma
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-10-30
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial tests the safety, side effects and best dose of radioligand therapy (lutetium Lu 177 PSMA-10.1 \[177Lu-rhPSMA-10.1\]) after prostate specific membrane antigen (PSMA) positron emission tomography (PET)-guided external beam radiotherapy in treating post-prostatectomy patients with prostate cancer that has come back after a period of improvement (recurrent). In this study, radioligand therapy is a radioactive drug called 177Lu-rhPSMA-10.1. It works by binding to PSMA-expressing prostate tumor cells and delivering the radioactive portion of the drug directly to the tumor cells while not harming normal cells. Radiation therapy such as external beam radiotherapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radioligand therapy with PSMA PET-guided external beam radiotherapy may kill more tumor cells in post-prostatectomy patients with biochemically recurrent prostate cancer.

Detailed description: PRIMARY OBJECTIVES:

I. Demonstrate the safety and feasibility of treating radiotherapy (RT) prostate cancer patients via addition of lutetium Lu 177 PSMA-10.1 (177Lu-rhPSMA-10.1) in a selected post-prostatectomy population.

II. Analyze dosimetry of radioligand therapy (RLT) after each cycle of 177Lu-rhPSMA-10.1.

EXPLORATORY OBJECTIVE:

I. Determine the feasibility of and develop preliminary data in the correlation of circulating tumor circulating tumor deoxyribonucleic acid (ctDNA) at baseline, after RT, and RLT.

OUTLINE: This is a dose-escalation study of 177Lu-rhPSMA-10.1.

Patients undergo external beam radiation therapy (EBRT) followed by 177Lu-rhPSMA-10.1 intravenously (IV) on study. Patients also receive flotufolastat F-18 (rhPSMA-7.3) IV with positron emission tomography (PET)/computed tomography (CT) at screening and undergo single-photon emission computed tomography (SPECT)-CT and collection of blood samples on study.

Patients follow up 6 weeks after the last 177Lu-rhPSMA-10.1 administration.

Eligibility criteria: Inclusion Criteria:

* Adenocarcinoma of the prostate, post radical prostatectomy with detectable prostate specific antigen (PSA)
* Clinical PSMA PET/CT obtained, with findings of pelvic uptake only (prostate bed, pelvic lymph node uptake, or both)
* Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2
* Age over 18

Exclusion Criteria:

* Contraindications to radiotherapy (including active inflammatory bowel disease or prior pelvic radiotherapy or prior RLT)
* Risk factors for Lu-rhPSMA radioligand therapy (Baseline \>= grade 2 myelosuppression, renal insufficiency \[glomerular filtration rate (GFR) \< 60 mL/min\], or xerostomia)
* Definitive findings of systemic metastasis prior imaging (if obtained) or biopsy (if obtained)
* Unacceptable medical or radiation safety risk
* Unmanageable urinary tract obstruction or hydronephrosis; patients with diagnosed or who are at high risk of urinary retention
* GFR \< 60 mL/min or creatinine \> 1.5-fold upper limit of normal (ULN)
* Liver enzymes \> 5-fold ULN
* Total white cell count less than 2.5 x 10\^9 /L
* Platelet count less than 75 x 10\^9 /L
* Any baseline grade 2 or above myelosuppression, nephrotoxicity, hepatotoxicity, xerostomia, or gastrointestinal (GI) toxicity
* Severe acute co-morbidity, defined as follows:

  * Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months
  * Transmural myocardial infarction within the last 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients

Primary outcomes:
measure: Incidence of radiotherapy and radioligand therapy related adverse events
timeFrame: Up to 6 weeks post last radioligand therapy dose
Secondary outcomes:
measure: Tumor and organ at risk dosimetry
timeFrame: At 1-3 days and 4-7 days post radioligand therapy
measure: Circulating tumor deoxyribonucleic acid (ctDNA) differences
timeFrame: Up to 5 years
measure: ctDNA differences
timeFrame: Up to 5 years
measure: ctDNA differences
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: David M Schuster, MD, FACR
role: PRINCIPAL_INVESTIGATOR
References: