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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Undergo collection of blood samples
Undergo PET/CT and SPECT/CT
Given IV
Given IV
Undergo PET/CT
Ancillary studies
Undergo SPECT/CT
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITING12-month overall survival
12-month overall survival (OS) of patients with mCRPC who previously had a favorable response to a first regimen of 177Lu-PSMA-617 and are treated with re-challenge 177Lu-PSMA-617 therapy
Time frame: Assessed at 12 months
Incidence of adverse events (AEs)
Overall and grade ≥ 3 AEs will be defined and graded according to Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be used to report the number and percentage of patients who experience AEs during re-challenge therapy. Separate statistics will be reported for grade ≥ 1 AEs and for grade ≥ 3 AEs. These descriptive statistics will be presented for the whole treatment as well as separately for each cycle. In addition, the relationship of AE to the study drug (related versus not related) will be reported. Results from laboratory test, physical examinations, and patient surveys will be used.
Time frame: Assessed approximately at 2 years
Rate of prostate specific antigen (PSA) response
Will be defined as a PSA decline of ≥ 50% during re-challenge therapy on two measurements ≥ 3 weeks apart. Descriptive statistics will be used to report the number and percentage of patients who had a PSA response to re-challenge therapy. The number and percentage of patients with any decrease in serum PSA level compared to the baseline PSA at time of study enrollment will be reported as well.
Time frame: Assessed approximately at 36 weeks
Biochemical progression-free survival (PFS)
Will be evaluated using Prostate Cancer Working Group 3 guidelines.
Time frame: Assessed approximately at 2 years
Overall Survival from start of first regimen
To determine OS from the start of the first regimen of 177Lu-PSMA-617 therapy (Cycle 1 Day 1) (each cycle is 6 weeks) through study completion.
Time frame: Assessed approximately at 2 years
Overall survival from the end of the first regimen
To determine OS from the end of the first regimen of 177Lu-PSMA-617 therapy (Day 1 of the final cycle) (each cycle is 6 weeks) through study completion.
Time frame: Assessed approximately at 2 years
Radiographic progression-free survival (rPFS)
To determine radiographic progression-free survival (rPFS) according to Response Evaluation Criteria in PSMA PET/CT (RECIP) criteria through study completion.
Time frame: approximately two years.
Bone Pain
Proportion of patients who initially had bone pain who experienced pain response with re-challenge 177Lu-PSMA-617 therapy
Time frame: approximately 36 weeks.
Changes in health-related quality of life_Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT).
The Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT) is a patient-reported outcome (PRO) tool designed to measure symptoms and toxicities among prostate cancer patients receiving radionuclide therapy (RNT). The total score can range from 0 to 60, with higher scores indicating better quality of life and fewer symptoms or side effects related to radionuclide therapy (RNT).
Time frame: approximately 36 weeks.
Changes in health-related quality of life_Brief Pain Inventory Short form
Pain response will be evaluated as at least a 2-point improvement from baseline without an overall increase in opiate use. evaluated using Brief Pain Inventory Short form (BPI-SF). The Brief Pain Inventory Short Form (BPI-SF) is a widely used tool for assessing pain severity and its impact on daily life. Ratings are on a scale from 0 (does not interfere) to 10 (completely interferes). The Pain Interference Score is the mean of these seven interference ratings, with a lower score being better.
Time frame: approximately 36 weeks.
Changes in health-related quality of life_ Eastern Cooperative Oncology Group score
To determine the impact of re-challenge 177Lu-PSMA-617 therapy on performance status using Eastern Cooperative Oncology Group score (ECOG) through re-challenge therapy completion. The ECOG Performance Status Scale is a widely used measurement in clinical oncology to assess a patient's level of functioning. It helps describe how a patient's disease impacts their daily living abilities. the ECOG scale ranges from 0 to 5. with a lower score indicating better daily living ability.
Time frame: approximately 36 weeks.
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