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

Prostate Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06216249
• Other study ID #: 23-000931
• Secondary ID: NCI-2023-07172
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2024
• Est. completion date: February 1, 2028

Study information

• Verified date: February 2024
• Source: Jonsson Comprehensive Cancer Center
• Contact: Stephanie Lira
• Phone: 310-206-0596
• Email: StephanieLira[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: February 1, 2028
• Est. primary completion date: February 1, 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have prostate cancer proven by histopathology

• Patients must have = 1 metastatic lesion by any imaging (CT, magnetic resonance imaging [MRI], bone scan, PET)

• Patients must have received at least one regimen of chemotherapy for mCRPC

• Patients must have received at least one androgen-receptor signaling inhibitors (ARSI)

• Patients must be eligible by PSMA PET VISION criteria. PSMA PET/CT must be performed within 8 weeks of planned first cycle of 177Lu-PSMA-617

• White blood cell (WBC) = 1500/ul

• Platelets (PLT) = 50.000/ul

• Hemoglobin (Hb) = 8.0 g/dl

• Absolute neutrophil count (ANC) = 1000 mm^3

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• Patients must be adults = 18 years of age

• Patients must have the ability to understand and sign an approved informed consent form (ICF)

• Patients must have the ability to understand and comply with all protocol requirements

Exclusion Criteria:

• Prior of 177Lu-PSMA-617 therapy

• Less than 6 weeks since last myelosuppressive therapy (including docetaxel, cabazitaxel, strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, hemi-body irradiation)

• Glomerular filtration rate (GFR) < 30 ml/min

• Urinary tract obstruction or marked hydronephrosis

Related Conditions & MeSH terms

• Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Procedure:
• Computed Tomography
Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT

Other:
• Gallium Ga 68 Gozetotide
Given IV

Drug:
• Lutetium Lu 177 Vipivotide Tetraxetan
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET/CT
• PSMA PET Scan
Undergo PSMA PET/CT

Other:
• Questionnaire Administration
Ancillary studies

Procedure:
• Single Photon Emission Computed Tomography
Undergo SPECT/CT

Locations

Country	Name	City	State
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year survival rate	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.	From the date of the first cycle of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen [PSMA]-617) therapy, up to 2 years
Secondary	Incidence of adverse events	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).	Up to 12 cycles and treatment holiday periods, assessed up to 24 months after first cycle of study treatment
Secondary	Overall survival	Group comparisons performed using appropriate tests including survival analyses (Kaplan-Meier estimator). Descriptive analyses (median, standard deviation) is used.	From the date of the first cycle injection of 177Lu-PSMA-617 until death, assessed up to 24 months after first cycle of study treatment
Secondary	Progression-free survival (PFS)	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.	The date of the first cycle injection of 177Lu-PSMA-617 to the date of first evidence of progression, or death from any cause, whichever occurs first, assessed up to 24 months after first cycle of study treatment
Secondary	Disease control rate (DCR)	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.	Up to 24 months after first cycle of study treatment
Secondary	DCR by combined radiographic + PSA response	Will be defined as PSA decline = 50% or radiographic PR/CR as defined above. Descriptive analysis will be used to determine the DCR.	Up to 24 months after first cycle of study treatment
Secondary	Bone pain level	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.	Up to 24 months after first cycle of study treatment
Secondary	Performance status	As measured by Eastern Cooperative Oncology Group (ECOG) performance status scale (minimum 0, maximum 5, with higher scores meaning a worse outcome)	Up to 24 months after first cycle of study treatment
Secondary	Health related quality of life (pain)	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).	Up to 24 months after first cycle of study treatment
Secondary	Health related quality of life (major symptoms/toxicities)	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).	Up to 24 months after first cycle of study treatment