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

NCT07200830 | Not Yet Recruiting Phase 3

• 1 other identifier: A032304
• Study Type: interventional
• Target: 1,524
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS)

  Will be calculated as time from randomization until death due to any cause, censoring patients not known to have died at the time of their last follow-up. OS will be compared between the treatment arms using a stratified log rank test

  Up to 5 years

• Quality of life

  Will be measured using the Functional Assessment of Cancer Therapy- Prostate (FACT-P) total scores. A repeated measures mixed model will be used to evaluate the between-arm mean difference in FACT-P Total scores across the first 30 months from treatment start. A point estimate of the difference and 95% confidence interval will be reported. Results of formal hypothesis testing will only be reported if adaptive dosing is deemed noninferior to standard dosing with regards to overall survival.

  Up to 30 months

Secondary Outcomes (7)

• Duration of treatment

  Up to 5 years

• Radiographic progression-free survival (rPFS)

  Up to 5 years

• Rate of Grade 3+ AEs

  Up to 5 years

• Prostate-specific antigen (PSA) response

  Prior to randomization

• Nadir PSA

  Up to 5 years

Other Outcomes (4)

• Frequency of tumor genomic aberrations

  Up to 3 months

• Association between initial PSA response and OS

  Up to 5 years

• Estimate of treatment effect by race

  up to 5 years

Study Arms (3)

Pre-registration step 0 (177Lu PSMA RLT)

ACTIVE COMPARATOR

Patients receive 177Lu PSMA RLT 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 C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.

Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Bone Scan; Procedure: PSMA PET Scan; Procedure: MRI; Other: Questionnaire Administration

Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)

ACTIVE COMPARATOR

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. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial

Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Bone Scan; Procedure: PSMA PET Scan; Procedure: MRI; Other: Questionnaire Administration

Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

EXPERIMENTAL

Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring 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 as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.

Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Biospecimen Collection; Procedure: Patient Monitoring; Procedure: Computed Tomography; Procedure: Bone Scan; Procedure: PSMA PET Scan; Procedure: MRI; Other: Questionnaire Administration

Interventions

Lutetium Lu 177 Vipivotide Tetraxetan DRUG

Given IV

Also known as: Pluvicto

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

Patient Monitoring PROCEDURE

Undergo PSA monitoring

Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan, CT Scan

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

Bone Scan PROCEDURE

Undergo Bone Scan

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

PSMA PET Scan PROCEDURE

Undergo PSMA PET Scan

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

MRI PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

Questionnaire Administration OTHER

Ancillary studies

Pre-registration step 0 (177Lu PSMA RLT); Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT); Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PRE-REGISTRATION (STEP 0): Patients must have histological, pathological, and/or cytological confirmation of prostate adenocarcinoma
• PRE-REGISTRATION (STEP 0): Patients must have a positive PSMA PET/CT scan (either gallium Ga 68 gozetotide \[68Ga-PSMA-11\], fluorine F 18 piflufolastat \[18F- DCFPyl\], or fluorine F 18 flotufolastat gallium \[18F-rhPSMA-7.3\]), as defined as uptake greater than liver with no PSMA negative measurable soft tissue disease
• PRE-REGISTRATION (STEP 0): PSA greater than 2.0 ng/mL
• PRE-REGISTRATION (STEP 0): Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
• Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
• Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions
• Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 Prostate Cancer Clinical Trials Working Group 3 \[PCWG3\] criteria, Scher et al 2016)
• PRE-REGISTRATION (STEP 0): Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
• PRE-REGISTRATION (STEP 0): Patients must have received at least one androgen receptor pathway inhibitor (ARPI) (to include either apalutamide, darolutamide, enzalutamide, or abiraterone)
• \* ARPI must be stopped at least 4 weeks prior to pre-registration
• PRE-REGISTRATION (STEP 0): Patients must not have previously received a taxane based chemotherapy regimen for mCRPC. Prior docetaxel for metastatic hormone-sensitive prostate carcinoma (mHSPC) or in the neoadjuvant or adjuvant setting is permitted if completed at least 12 months prior to pre-registration
• PRE-REGISTRATION (STEP 0): Patients must have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.)
• PRE-REGISTRATION (STEP 0): Patients on a stable bisphosphonate or denosumab regimen for ≥ 30 days prior to pre-registration are eligible
• PRE-REGISTRATION (STEP 0): Previous treatment with strontium Sr-89 (strontium-89), samarium Sm-153 (samarium-153), rhenium Re 186 (rhenium-186), rhenium Re 188 (rhenium-188), radium Ra 223 (radium-223) or hemi-body irradiation within 6 months prior to pre-registration is not allowed. Previous PSMA-targeted radioligand therapy is not allowed
• PRE-REGISTRATION (STEP 0): Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 28 days prior to pre-registration is not allowed

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; Remote Patient Monitoring; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Telemedicine; Delivery of Health Care; Patient Care Management; Health Services Administration; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Thomas Hope, MD

  Alliance for Clinical Trials in Oncology

  STUDY CHAIR

Central Study Contacts

Shiva Baghaie, MPH

CONTACT

773-702-9171; GUprotocols@alliancenctn.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: October 1, 2025
• Study Start: October 8, 2025
• Primary Completion (Estimated): September 9, 2034
• Study Completion (Estimated): September 9, 2034
• Last Updated: October 1, 2025

Record last verified: 2025-09