NCT07200830

Testing Different Dosing Schedules of the Anti-cancer Drug, Lutetium 177Lu PSMA RLT and Its Effect on Patients With Advanced Prostate Cancer, RECIPROCAL Trial

Radioligand Efficacy Comparison by Initial PSA-Response Outcome in Metastatic CRPC With Lutetium 177Lu PSMA RLT (RECIPROCAL)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,524 (estimated)
• Sponsor: Alliance for Clinical Trials in Oncology · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase III trial examines whether lengthening the dosage interval in an adaptive manner for the prostate cancer drug lutetium 177 Lu PSMA RLT improves quality of life without decreasing lifespan when compared to the standard way this medication is given. This study is for patients with hormone resistant prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body. Hormone resistant prostate cancer often has many cells containing a protein called prostate-specific membrane antigen (PSMA) on their surface. The normal cells in the prostate do not normally express as much PSMA protein on their surface as cancer cells. Lutetium 177 Lu PSMA RLT binds to the PSMA protein on the tumor cells. It builds up in these cells and gives off radiation that may kill them. Typically, this medication is given at the same dose every 6 weeks for up to 6 doses. In this trial, researchers want to see if treatment following the first two doses of lutetium 177 Lu PSMA RLT can be delayed until there is evidence of disease activity. This may be an effective way to improve quality of life without decreasing lifespan in patients with advanced prostate cancer.

Detailed description

The primary and secondary objectives of the study: PRIMARY OBJECTIVES: I. To compare the overall survival (OS) of patients with metastatic castration-resistant prostate carcinoma (mCRPC) receiving prostate-specific antigen (PSA) adaptive dosing of lutetium 177 Lu prostate specific membrane antigen radioligand therapy (177Lu PSMA RLT) to that of patients receiving standard dose 177Lu PSMA RLT every 6 weeks. II. To compare quality of life, as measured by Functional Assessment of Cancer Therapy- Prostate (FACT-P) total scores averaged across the first 30 months, in patients with mCRPC who receive 177Lu PSMA RLT adaptive dosing versus standard dosing. SECONDARY OBJECTIVES: I. To compare the duration of treatment between standard dosing and adaptive dosing. II. To compare the radiographic progression-free survival (rPFS) between the treatment arms. III. To evaluate and compare the toxicity profile of 177Lu PSMA RLT standard dosing and 177Lu PSMA RLT adaptive dosing. IV. To compare the nadir PSA and PSA kinetics between standard and adaptive dosing. V. To compare quality-adjusted life years, which accounts for overall survival and health utility (measured by European Quality of Life Five Dimension Five Level Scale \[EQ-5D-5L\]), between arms. VI. To compare pain severity, as measured by the Brief Pain Inventory - Short Form (BPI-SF), between arms at 12 and 30 months. EXPLORATORY OBJECTIVES: I. To determine the frequency of tumor genomic aberrations (including but not limited to androgen receptor \[AR\] mutation/amplification, deoxyribonucleic acid \[DNA\] repair, retinoblastoma 1 \[RB1\], phosphatase and tensin homolog \[PTEN\], TP53) by circulating-tumor deoxyribonucleic acid (ctDNA) in patients achieving \> 50% PSA decline versus (vs) \< 50% PSA decline after 2 cycles of 177Lu PSMA RLT. II. To evaluate the relationship between OS and initial PSA response (e.g. ≥ 50% decline in PSA level from baseline \[PSA50\] vs ≥ 75% decline in PSA level from baseline \[PSA75\] vs ≥ 90% decline in PSA level from baseline \[PSA90\]) prior to randomization. OUTLINE: PRE-REGISTRATION STEP 0: Patients receive 177Lu PSMA RLT intravenously (IV) on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at cycle (C) 2 day (D) 22 proceed to Step 1. RANDOMIZATION STEP 1: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM 2: Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring once every 3 weeks (Q3W) in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise \> 4 ng/dL, PSA rise \> 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, all patients undergo blood sample collection, computed tomography (CT), and bone scan throughout the trial and PSMA positron emission tomography (PET) during screening. Patients with a history of brain metastases or with clinical indication also undergo magnetic resonance imaging (MRI) throughout the trial. After completion of study treatment, patients are followed up every 12 weeks until disease progression and then every 6 months thereafter for 5 years following registration.

Conditions

• Metastatic Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Adenocarcinoma
• Stage IVB Prostate Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Lutetium Lu 177 Vipivotide Tetraxetan	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Patient Monitoring	Undergo PSA monitoring
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Bone Scan	Undergo Bone Scan
PROCEDURE	PSMA PET Scan	Undergo PSMA PET Scan
PROCEDURE	MRI	Undergo MRI
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2025-10-08
• Primary completion: 2034-09-09
• Completion: 2034-09-09
• First posted: 2025-10-01
• Last updated: 2025-10-01