STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer

Trial Title: STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer

NCT ID: NCT06574880

Condition: Malignant Neoplasm of Prostate
Locally Advanced Prostate Cancer

Conditions: Official terms:
Prostatic Neoplasms
Neoplasms

Conditions: Keywords:
Prostate cancer

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Lu-PSMA-617
Description: Lu-PSMA will be administered at a fixed dose of 7.4GBq per cycle, on a dose escalation schedule: - Level 0: Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT. - Level 1 (Starting Dose Level): Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT, followed 6 weeks later by cycle 2. - Level 2: Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT, followed 6 weeks later by cycle 2, followed 6 weeks later by cycle 3.
Arm group label: Lu-PSMA-617 + SBRT

Other name: Pluvicto

Intervention type: Radiation
Intervention name: 5-fraction Stereotactic Body Radiation Therapy (SBRT)
Description: Prostate and nodal SBRT will begin at the completion of cycle 1 (6 weeks after the first Lu-PSMA-617 infusion, ± 4 weeks).
Arm group label: Lu-PSMA-617 + SBRT

Other name: SBRT

Summary: The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer. Participants will receive one dose of Pluvicto, followed by radiation about 6 weeks later. Radiation therapy will be completed in 5 treatments over the period of 2 weeks. A second dose of Pluvicto will be given 6 weeks after radiation is complete. Some participants may also receive a third dose of Pluvicto, and this would be given 6 weeks after the second dose of Pluvicto.

Detailed description: Prostate cancer is the most common cancer in men worldwide and second leading cause of cancer death in men. The most common treatment for prostate cancer is radiation therapy (RT) plus long-term androgen deprivation therapy (ADT) for 18-36 months with a consideration for the addition of abiraterone acetate. With the introduction of abiraterone and other second generation androgen signaling inhibitors (ARSIs) there is great interest in shortening the duration of systemic therapy. This interest stems from the high toxicity rates of ADT and substantial impact on patient-reported quality of life (QoL). The use of ADT is associated with some adverse events. Therefore, the combination of adverse event risks and decrease in quality of life associated with castration have resulted in decreased compliance to long term ADT and even ARSIs, where approximately 50% of patients with locally advanced disease either decline any ADT or stop treatment early. The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer. This clinical trial will evaluate the safety of using Lu-PSMA-617 with SBRT to the prostate and pelvic lymph nodes, and to determine whether Lu-PSMA-617 can replace androgen deprivation therapy (ADT) to improve oncologic outcomes by use of cytotoxic agents, avoid ADT related side effects, and improve compliance for participants to receive systemic therapy.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Participant must be ≥ 18 years of age. - ECOG performance status ≤ 1 - Histologic confirmation of prostate adenocarcinoma of the prostate - PSMA avid disease on PSMA PET/CT, where the tumor in the prostate has SUVmax ≥ 10. - PSMA PET/CT must be obtained within 4 months. - Need ≥ 1 criteria: - Node positive disease on PSMA PET/CT or conventional imaging, as defined by having any of the following: - Pelvic nodal disease (cN1) as defined by LN stations that commence at the bifurcation of the common iliac vessels - Regional nodal disease (M1a) as defined by LN stations that commence at the bifurcation of the aorta and bifurcation of the proximal inferior vena cava to the common iliac veins. - In the absence of nodal metastasis, must have ≥ 2 of the following - i. cT3a or cT3b by conventional imaging (MRI) or PSMA PET/CT - ii. Grade group ≥ 4 - iii. PSA ≥ 40 ng/mL - Adequate organ and marrow function to receive treatment: - Hemoglobin > 10 g/dL - White blood cell (WBC) > 3000 / mL - Absolute neutrophil count ≥ 1,500 / mcL - Platelets ≥ 100,000 / mcL - Creatinine ≤ 1.5x ULN - Estimated glomerular filtration rate (eGFR)* > 50 mL/min - Total bilirubin** < 2× ULN - Albumin > 3 g/dL - Aspartate aminotransferase (AST) < 3× ULN - *based upon Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Participants with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only participants with non-obstructive pathology will be included in the study. - ** Total bilirubin ≤ 2x ULN (except for participants with known Gilbert's Syndrome ≤ 3x ULN is permitted) - International Prostate Symptoms Score (IPSS) ≤ 15. - Medically fit for treatment and agreeable to follow-up. - Ability to understand and the willingness to sign a written informed consent. - Participants with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 14 weeks from receiving the last dose of Lu-PSMA-617. Participants must also not donate sperm for 14 weeks from receiving the last dose of Lu-PSMA-617. Exclusion Criteria: - Clinical or radiographic evidence of distant metastatic disease (M1a above aortic bifurcation, M1b, or M1c) by any imaging. Participants are allowed to M1a nodal disease that is below the aortic bifurcation. Negative PSMA PET/CT is an acceptable substitute to conventional staging. - Prostate gland size >90 cc measured by ultrasound or MRI - Prior head and neck radiation therapy. - Prior treatment for prostate cancer (incudes chemotherapy, radiation therapy, or anti-androgen therapy). - Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies. - Prohibited 3 months before participant registration and during administration of study treatment: oral ketoconazole, chemotherapy, immunotherapy, estrogens, and radiopharmaceuticals. - History of prior pelvic radiation therapy. - Enrollment concurrently in another investigational drug study within 6 months of registration. - History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer. - History of prior hematologic malignancies, including myelodysplastic syndrome or leukemia. - History of or active Crohn's disease or ulcerative colitis. - Contraindication to or inability to tolerate PSMA/PET. - Any condition that in the opinion of the investigator would preclude participation in this study.

Gender: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center

Address:
City: Cleveland
Zip: 44106
Country: United States

Start date: March 11, 2025

Completion date: September 11, 2026

Lead sponsor:
Agency: Angela Y. Jia, MD PhD
Agency class: Other

Source: Case Comprehensive Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06574880