Re-treatment With 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer, RE-LuPSMA Trial

Official title

Re-Treatment With 177Lu-PSMA-617 Molecular Radiotherapy for Metastatic Castration Resistant Prostate Cancer: A Prospective Phase 2 Trial (RE-LuPSMA STUDY)

Overview

This phase II trial tests how well re-treatment with 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic), that continues to grow or spread after the surgical removal of the testes or medical treatment to block androgen production (castration-resistant), and that has shown a favorable response to initial treatment with 177Lu-PSMA-617. 177Lu-PSMA-617 is a radioactive drug. It binds to a protein called prostate specific membrane antigen (PSMA), which is expressed by some types of prostate tumor cells. When 177Lu-PSMA-617 binds to PSMA-expressing tumor cells, it delivers radiation to the cells, which may kill them. Re-treatment with 177Lu-PSMA-617 in patients who had a favorable response to initial 177Lu-PSMA-617 treatment may improve survival outcomes and disease response in patients with metastatic castration-resistant prostate cancer.

Detailed description

PRIMARY OBJECTIVE:

I. To assess the treatment efficacy of re-challenge lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) therapy (for a maximum of 6 additional cycles) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had a favorable response to a prior regimen of 177Lu-PSMA-617 therapy.

SECONDARY OBJECTIVES:

I. To determine the safety of re-challenge 177Lu-PSMA-617 therapy by Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

II. To determine the rate of patients who have a prostate-specific antigen (PSA) response (defined as a PSA decline of ≥ 50% during re-challenge 177Lu-PSMA-617 therapy).

III. To determine biochemical progression-free survival (PFS) according to Prostate Cancer Working Group 3 (PCWG3) guidelines.

IV. To determine overall survival (OS) from the start (cycle 1 day 1) of the first regimen of 177Lu-PSMA-617 therapy.

V. To determine OS from the end (day 1 of the final cycle) of the first regimen of 177Lu-PSMA-617 therapy.

VI. To determine radiographic progression-free survival (rPFS) according to Response Evaluation Criteria in PSMA positron emission tomography (PET)/computed tomography (CT) (RECIP) criteria.

VII. To determine the impact of re-challenge 177Lu-PSMA-617 therapy on bone pain level, health-related quality of life, and performance status (Eastern Cooperative Oncology Group \[ECOG\]) using established standardized questionnaires.

EXPLORATORY OBJECTIVE:

I. To determine the dosimetry in organs and tumor lesions of re-challenge 177Lu-PSMA-617 therapy using a 24-hour single-time-point dosimetry protocol.

OUTLINE:

Patients receive 177Lu-PSMA-617 intravenously (IV) on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive gallium Ga 68 gozetotide IV and undergo PET/CT at screening and on study, undergo single photon emission computed tomography (SPECT)/CT on study, and undergo collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up within 8 weeks of their last treatment cycle and then every 3 months for up to a total of 2 years.

Interventions

• Procedure Biospecimen Collection
  Undergo collection of blood samples
• Procedure Computed Tomography
  Undergo PET/CT and SPECT/CT
• Other Gallium Ga 68 Gozetotide
  Given IV
• Drug Lutetium Lu 177 Vipivotide Tetraxetan
  Given IV
• Procedure Positron Emission Tomography
  Undergo PET/CT
• Other Questionnaire Administration
  Ancillary studies
• Procedure Single Photon Emission Computed Tomography
  Undergo SPECT/CT

Primary outcome measures

• 12-month overall survival [Time frame: Assessed at 12 months]

Secondary outcome measures (10)

• Incidence of adverse events (AEs) [Time frame: Assessed approximately at 2 years]
• Rate of prostate specific antigen (PSA) response [Time frame: Assessed approximately at 36 weeks]
• Biochemical progression-free survival (PFS) [Time frame: Assessed approximately at 2 years]
• Overall Survival from start of first regimen [Time frame: Assessed approximately at 2 years]
• Overall survival from the end of the first regimen [Time frame: Assessed approximately at 2 years]
• Radiographic progression-free survival (rPFS) [Time frame: approximately two years.]
• Bone Pain [Time frame: approximately 36 weeks.]
• Changes in health-related quality of life_Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT). [Time frame: approximately 36 weeks.]
• Changes in health-related quality of life_Brief Pain Inventory Short form [Time frame: approximately 36 weeks.]
• Changes in health-related quality of life_ Eastern Cooperative Oncology Group score [Time frame: approximately 36 weeks.]

Eligibility criteria

Inclusion criteria

• Patients must have mCRPC
• Patients must have received at least one regimen of chemotherapy for mCRPC
• Patients must have received at least one androgen receptor signaling inhibitor (ARSI)
• Patients must have previously completed at least 4 cycles of 177Lu-PSMA-617 therapy
• Patients must have had a favorable response to the first regimen of 177Lu-PSMA-617 therapy defined as:

• PSA decline of ≥ 50% at any time during the first regimen of 177Lu-PSMA-617 therapy AND
• No new prostate cancer therapy within two months of completing the first regimen of 177Lu-PSMA-617 therapy (first-generation androgen deprivation therapy \[ADT\] is allowed). Concomitant prostate cancer therapy that was administrated during the first regimen of 177Lu-PSMA-617 therapy and continued afterwards is allowed
• Patients must have had a PSA increase after the first regimen of 177Lu-PSMA-617 therapy, confirmed by a second measurement ≥ 3 weeks apart
• Patients must meet PSMA PET/CT VISION criteria. PSMA PET/CT must have been completed within 8 weeks of the planned first cycle of re-challenge 177Lu-PSMA-617 therapy and at least 6 weeks after completion of the first regimen of 177Lu-PSMA-617 therapy
• White blood cells > 2,500 cells/µL
• Absolute neutrophil count > 1,500 cells/µL
• Hemoglobin > 9.0 g/dL
• Platelets > 100,000 cells/µL
• Patients must have the ability to understand and sign an approved informed consent form (ICF) and comply with all protocol requirements

Exclusion criteria

• Patient received new prostate cancer therapy within two months of completing the first regimen of 177Lu-PSMA-617 therapy (first-generation ADT (adenosine triphosphate) is allowed). This can include apalutamide, enzalutamide, abiraterone, chemotherapy, immunotherapy, radionuclide therapy, PARP inhibitor, or any biological therapy. Concomitant prostate cancer therapy that was administrated during the first regimen of 177Lu-PSMA-617 therapy and continued afterwards is allowed
• Patient received myelosuppressive therapy (including docetaxel, cabazitaxel, 223Ra, and 153Sm) or other radionuclide therapy within the last 6 weeks
• Patient with creatinine clearance < 50 mL/min

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• UCLA / Jonsson Comprehensive Cancer Center — Los Angeles

Publications

• Nikitas J, Holzgreve A, Juarez J, Kimura K, Lira S, Alam H, Contreras M, Theus L, Nguyen AT, Ells Z, Zhu S, Grogan T, Elashoff DA, Unterrainer LM, Dahlbom M, Allen-Auerbach M, Czernin J, Calais J. Phase 2 Prospective Trial of Retreatment with [177Lu]Lu-PSMA-617 Molecular Radiotherapy for Metastatic Castration-Resistant Prostate Cancer-RE-LuPSMA. J Nucl Med. 2026 May 1;67(5):674-680. doi: 10.2967/j PMID 41679923

Identifiers

NCT: NCT06288113 · 23-001509 · NCI-2024-00310 · 23-001509

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗