Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Carcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Infective Agents

Anticoagulants

Bone Density Conservation Agents

Amino Acids

Gallium 68 PSMA-11

Pluvicto

Carbamide Peroxide

Edetic Acid

Pentetic Acid

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Chelating Agents

Calcium

Calcium, Dietary

Radiopharmaceuticals

Lysine

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT

Computed Tomography

Gallium Ga 68 Gozetotide

Lutetium Lu 177 Vipivotide Tetraxetan

Positron Emission Tomography

PSMA PET Scan

Questionnaire Administration

Single Photon Emission Computed Tomography

Stephanie Lira

Jeremie Calais

The randomized phase 2 FLEX MRT compares a group of patients treated with LuPSMA on a flexible and extended dosing schedule including "treatment holiday" periods (investigational arm, up to 12 cycles) to a control group treated with a fixed dosing schedule of 6 treatments cycles maximum administered every 6 weeks.

The flexible dosing schedule in the investigational arm, will be based on SPECT/CT response assessments obtained 24h after injection of LuPSMA therapy cycle. The response assessment during treatment holiday period will be based on PET/CT every 12 weeks.

PRIMARY OBJECTIVE:

I. To assess a potential survival benefit (2-year survival rate) of patients treated with Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) therapy on a flexible dosing schedule including up to 12 cycles and potential "treatment holiday" periods in comparison to patients treated with the standard fixed dosing schedule of maximum 6 treatment cycles every 6 weeks.

SECONDARY OBJECTIVES:

I. To determine the safety of the flexible/extended schedule of 177Lu-PSMA-617 therapy.

II. To compare the overall survival (OS) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

III. To compare the progression-free survival (PFS) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

IV. To compare the disease control rate (DCR) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

V. To compare the impact on bone pain level of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

VI. To compare the impact on health-related quality of life of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

EXPLORATORY OBJECTIVE:

I. To determine the dosimetry in organs and tumor lesions of the flexible/extended schedule of 177Lu-PSMA-617 therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive 177Lu-PSMA-617 intravenously (IV) once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68 gozetotide (68Ga-PSMA-11) IV and undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) throughout the trial. Patients also undergo single photon emission computed tomography (SPECT)/CT, PET/CT, or CT on the trial.

ARM II: Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Upon completion of study treatment, patients are followed up every 3 months for 24 months from after first cycle of study treatment.

Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)

A Phase 2 Randomized Trial in Patients With Metastatic Castration Resistant Prostate Cancer to Determine the Efficacy of a Flexible Dosing Schedule of Lu-PSMA Treatment up to 12 Cycles Including Potential Treatment Holiday Periods in Comparison to the Standard Fixed Dosing Schedule of Six Cycles Every Six Weeks (FLEX-MRT)

Will be assessed patients treated with 177Lu-PSMA-617 therapy on a flexible dosing schedule (investigational arm) in comparison to patients treated with the standard fixed dosing schedule of maximum 6 treatments cycles every 6 weeks (control arm). Will be reported using descriptive statistics by means of number and percentage of patients dead 24 months after the first cycle.

Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE). Descriptive statistics (number and percentage) will be reported separately for adverse events (AE) in total and serious adverse events (SAE) based on CTC. These descriptive statistics will be presented for the whole treatment as well as separate for each cycle. In addition, the relationship of AE to the study drug (related, not related) will be reported. Both results from laboratory test, physical examinations and patients surveys will be included. Distribution of each result will be compared between both groups using appropriate tests (e.g., Mann-Whitney U test).

Group comparisons performed using appropriate tests including survival analyses (Kaplan-Meier estimator). Descriptive analyses (median, standard deviation) is used.

Group comparisons performed using appropriate tests including survival analyses (Kaplan-Meier estimator). Descriptive analyses (median, standard deviation) is used. Radiographic progression defined as the date of progression on single photon emission computed tomography (SPECT) by visual increase in tumor volume ≥ 30% compared to baseline ± new sites of disease and/or new sites of prostate-specific membrane antigen (PSMA)-negative disease progression on diagnostic computed to computed tomography (CT) or on PSMA positron emission tomography (PET)/CT. Prostate specific antigen (PSA) progression is the date when a ≥ 25% increase in PSA and an increase of 2 ng/mL or more from the nadir is documented and confirmed by a second consecutive value obtained 3 or more weeks later. Clinical progression defined as marked escalation in cancer related pain, immediate need for initiation of new anticancer treatment, and marked deterioration in Eastern Cooperative Oncology Group (ECOG) performance.

Will be defined as the proportion of patients achieving radiographic stable disease (SD), partial response (PR) or complete response (CR). CR is defined as absence of PSMA-avid tumor on either imaging modality. On SPECT/CT, PR is defined as a \> 30% reduction in visual tumor volume at all sites of involved disease compared to baseline cycle #1, no new sites of PSMA-avid tumor and no new sites of PSMA-negative tumor on diagnostic CT, and SD is defined as no change \> 30% in visual tumor volume compared to baseline cycle #1, no new sites of PSMA-avid tumor and no new sites of PSMA-negative tumor on diagnostic CT. Respective response groups on PSMA PET/CT are defined by Response Evaluation Criteria in Prostate-specific membrane antigen PSMA PET/CT criteria. Descriptive analysis will be used to determine the DCR.

Will be defined as PSA decline ≥ 50% or radiographic PR/CR as defined above. Descriptive analysis will be used to determine the DCR.

Descriptive analysis will be used to evaluate the impact on bone pain level by determining the proportion of patients with pain response defined by improvement from baseline (all patients with ≥ 4/10) of at least 2-point absolute improvement without an overall increase in opiate use.

As measured by Eastern Cooperative Oncology Group (ECOG) performance status scale (minimum 0, maximum 5, with higher scores meaning a worse outcome)

Will be reported using the Brief Pain Inventory - Short Form patient reported outcome questionnaire (9 questions including scales; minimum 0, maximum 10, with higher scores meaning a worse outcome).

Will be reported using the Functional Assessment of Cancer Therapy - Radionuclide Therapy patient reported outcome questionnaire (15 questions; minimum 0, maximum 5, with higher scores meaning a worse outcome).

Jonsson Comprehensive Cancer Center

Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

Biospecimen Collection

Bone Scan

Clinical Observation

Clinical Trials Referral Office

Matthew P. Thorpe, M.D., Ph.D.

This phase II trial studies how to improve the usage of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen \[PSMA\]-617) for treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site), to other places in the body (metastatic) utilizing a treatment pause after 5 cycles of therapy versus standard continuous treatment for 6 cycles. Lutetium is a radioligand therapy (RLT). RLT uses a small molecule (in this case 177Lu-PSMA-617) that carries a radioactive component to destroy tumor cells. When lutetium is injected into the body, it attaches to the PSMA receptor found on tumor cells. After lutetium attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving 177Lu-PSMA-617 for 5 cycles versus 6 cycles may better treat patients with metastatic castrate resistant prostate cancer.

PRIMARY OBJECTIVES:

I. To determine whether progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria is non-inferior among patients randomized to treatment pause versus standard treatment in patients with metastatic castrate resistant prostate cancer (mCRPC) who have minimal residual disease on post-therapy single photon emission computed tomography (SPECT) after 2 to 5 cycles of 177Lu-PSMA-617 treatment.

SECONDARY OBJECTIVES:

I. To compare time to subsequent treatment (TTST) in this patient population between randomized arms.

II. To assess time to progression (TTP) between randomized arms in this patient population between randomized arms.

III. To assess overall survival (OS) in this patient population between randomized arms.

IV. To compare toxicities in treatment pause versus standard treatment in this patient population.

V. To assess changes in patient quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACIT-RNT) for each randomized arm.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive 177Lu-PSMA-617 intravenously (IV) over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive 68Ga-prostate specific membrane antigen-11 (gallium Ga 68-labeled PSMA-11) IV and undergo positron emission tomography (PET)/computed tomography (CT) and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

ARM II: Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

ARM III: Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

After completion of study treatment, patients are followed up every 12 weeks for up to 2 years or progressive disease.

Schedule De-Escalation of 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer

Minority-Inclusive Imaging Biomarker-Based End of Therapy Trial for 177Lu-PSMA-617, a Randomized De-Escalation Theranostic Trial for Metastatic Castrate Resistant Prostate Cancer

Progression free survival is defined as the time interval between randomization date and the date of disease progression or death, whichever occurs first. Progression will be defined in keeping with Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines. The median progression free survival of each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.

TTST is defined as the time from randomization to subsequent treatment. Median TTST will be estimated using the Kaplan-Meier method. Patients who do not progress to a subsequent treatment while on study will be censored at the last known follow-up date. The median TTST and corresponding 95% confidence interval will be reported by randomized arm. The log-rank test will be used to compare the two arms on the distribution of TTST.

TTP is defined as the time from randomization to disease progression. Median TTP will be estimated using the Kaplan-Meier method. Patients who do not experience disease progression while on study will be censored at the last disease assessment date. Deaths will be censored. The median TTP and corresponding 95% confidence interval will be reported by randomized arm. The log-rank test will be used to compare the two arms on the distribution of TTP.

Overall survival is defined as the time from study entry to death from any cause. Vital status and death dates will be obtained be electronic medical record review where possible, and by phone call where unavailable. Median OS will be estimated using the Kaplan-Meier method. Patients who do not experience death while on study will be censored at the last known date alive. The median OS and corresponding 95% confidence interval will be reported by randomized arm. The log-rank test will be used to compare the two arms on the distribution of OS.

Adverse events will be summarized by frequency and severity using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. The proportion of patients who experience a grade 3+ adverse event at least possibly related to treatment will be reported by arm.

Will be collected using the Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT). The FACT-RNT is a 15-item measure assessing symptoms and toxicities on a 0-4 scale. Total scores range from 0-60, with higher scores indicating better quality of life. Mean values at each collection timepoint will be plotted and stratified by randomized arm.

Mayo Clinic

Patients receive 177Lu-PSMA-617 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 SPECT/CT on study, and undergo collection of blood samples throughout the trial.

Ethan Lam

Jeremie Calais, MD

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.

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

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

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

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.

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.

Will be evaluated using Prostate Cancer Working Group 3 guidelines.

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.

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.

To determine radiographic progression-free survival (rPFS) according to Response Evaluation Criteria in PSMA PET/CT (RECIP) criteria through study completion.

Proportion of patients who initially had bone pain who experienced pain response with re-challenge 177Lu-PSMA-617 therapy

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).

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)	NCT06216249	Prostate Carcin... Stage IVB Prost...	Computed Tomogr... Gallium Ga 68 G... Lutetium Lu 177... Positron Emissi... PSMA PET Scan Questionnaire A... Single Photon E...	18 Years -	Jonsson Comprehensive Cancer Center
Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)	NCT06216249	Prostate Carcin... Stage IVB Prost...	Computed Tomogr... Gallium Ga 68 G... Lutetium Lu 177... Positron Emissi... PSMA PET Scan Questionnaire A... Single Photon E...	18 Years -	Jonsson Comprehensive Cancer Center
Schedule De-Escalation of 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer	NCT06200103	Castration-Resi... Stage IVB Prost...	Biospecimen Col... Bone Scan Clinical Observ... Computed Tomogr... Gallium Ga 68 G... Lutetium Lu 177... Positron Emissi... Questionnaire A... Single Photon E...	18 Years -	Mayo Clinic
Re-treatment With 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer, RE-LuPSMA Trial	NCT06288113	Castration-Resi... Stage IVB Prost...	Biospecimen Col... Computed Tomogr... Gallium Ga 68 G... Lutetium Lu 177... Positron Emissi... Questionnaire A... Single Photon E...	-	Jonsson Comprehensive Cancer Center

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