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

This phase IV studies how to improve the use 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 versus standard continuous 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Castration-Resistant Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Procedure: Single Photon Emission Computed Tomography; Other: Gallium Ga 68 Gozetotide; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Other: Clinical Observation

Detailed Description

PRIMARY OBJECTIVES:

To determine whether progression-free survival (PFS) 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 5 cycles of 177Lu-PSMA-617 treatment.

SECONDARY OBJECTIVES:

I. To assess time to subsequent treatment (TTST) in this patient population for each randomized arm.

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

III. To assess overall survival (OS) in this patient population for each randomized arm.

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

OUTLINE: Patients are randomized to 1 of 2 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 6 cycles in the absence of disease progression or unacceptable toxicity. 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. Patients may resume treatment with 77Lu-PSMA-617. 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 who achieved complete response, partial response, or stable disease are followed up at 3 months, then every 3 months for 1 year, and then every 6 months for up to 3 years from time of registration.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Matthew P. Thorpe, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• REGISTRATION INCLUSION CRITERIA
• Histologically confirmed diagnosis of prostate cancer
• Referred to Mayo Clinic Rochester for therapy with 177Lu PSMA-617
• PSMA positive metastatic castration resistant prostate cancer (68Ga and 18F PSMA PET will be considered equivalent for eligibility) , defined by molecular imaging prostate specific membrane antigen (miPSMA) score >= 2 on Mayo PET report, including interpretation of outside PET

• Prior treatment: Patients must meet FDA label indication, having previously received:

  • Androgen receptor pathway inhibition (abiraterone acetate, apalutamide, enzalutamide, darolutamide, or investigational androgen receptor targeted therapy)
  • Taxane based chemotherapy (docetaxel and/or cabazitaxel)
• Willingness to provide mandatory blood draws for correlative research. (This requirement is waived for patients enrolling after receiving cycle 1 of 177Lu PSMA-617, as these patients will not be able to provide a pre-treatment baseline blood sample.)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2. (Make sure to list the possible options 0,1 or 2 and not as a range per Study Build)
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 30 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 30 days prior to registration)
• Platelet count ≥ 100,000/mm^3 (obtained ≤ 30 days prior to registration)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 30 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 30 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained ≤ 30 days prior to registration)
• Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (obtained ≤ 30 days prior to registration)
• Provide written informed consent
• Ability to complete questionnaire(s) by themselves or with assistance
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• RANDOMIZATION INCLUSION CRITERIA
• Visible lesions on cycle 1 post therapy SPECT, demonstrating that a negative follow up post-therapy scan is attributable to response, rather than sensitivity differences between pre-treatment PET
• Near-complete response on post-therapy SPECT following cycles 2-5 of 177Lu PSMA-617. Near-complete response will be defined as no lesions with SUV max above the mean SUV of a representative 2cm spherical region of interest in the central right hepatic lobe, as determined by a nuclear medicine trained radiologist blind to the locations of previously PSMA avid lesions
• No toxicity that would indicate withholding or reducing dose of the next scheduled cycle of 177Lu PSMA-617 per prescribing information
• Hemoglobin (Hgb) < 10 g/dL
• Platelets < 75,000/mm^3
• Neutrophils < 1500/mm^3
• Glomerular filtration rate (GFR) < 30 mL/min using Cockcroft-Gault formula
• Creatinine > 1.5x baseline patient-specific baseline, defined as average of 2 prior measurements (if available)
• Dry mouth limiting oral intake to purees or soft/moist foods
• Diarrhea, nausea or constipation causing inability to complete instrumental activities of daily living (ADL) or requiring medical intervention to maintain hydration and alimentation
• Fatigue not relived by rest, limiting instrumental ADL
• AST or ALT > 5x upper limit of normal
• Other unacceptable toxicity in the clinical judgement of the investigators
• RE-REGISTRATION INCLUSION CRITERIA (CROSSOVER TO COMPLETION UPON FIRST PROGRESSION OF PATIENTS RANDOMIZED TO TREATMENT PAUSE)
• First progression in patients randomized to pause treatment
• PSMA avid lesions on PSMA PET (miPSMA score ≥ 2 within 30 days of resuming therapy)

Exclusion Criteria:

• REGISTRATION EXCLUSION CRITERIA
• Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy
• Receiving any other investigational agent which would be considered as a treatment for the prostate cancer

• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment

  • EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment

• Uncontrolled intercurrent non-cardiac illness including, but not limited to:

  • Ongoing or active infection
  • Psychiatric illness/social situations
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
  • Any other conditions that would limit compliance with study requirements

• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy

  • NOTE: Patients known to be human immunodeficiency virus (HIV) positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

• Any of the following because this study involves: An investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

  • Persons able to father a child who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• RE-REGISTRATION EXCLUSION CRITERIA
• Serious adverse effect

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (177Lu-PSMA-617 standard); 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.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Single Photon Emission Computed Tomography; Undergo SPECT/CT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Other: Gallium Ga 68 Gozetotide; Given IV; Other Names: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC; (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68Ga)Glu-urea-Lys(Ahx)-HBED-CC; 68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-PSMA; 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; 68Ga-PSMA; 68Ga-PSMA-11; 68Ga-PSMA-HBED-CC; [68Ga] Prostate-specific Membrane Antigen 11; [68Ga]GaPSMA-11; Ga PSMA; Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled PSMA-11; GA-68 PSMA-11; Gallium Ga 68 PSMA-11; Gallium Ga 68-labeled PSMA-11; GALLIUM GA-68 GOZETOTIDE; Gallium-68 PSMA; Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; GaPSMA; PSMA-HBED-CC GA-68; AAA 517; AAA-517; AAA517; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Computed Tomography; Undergo SPECT/CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Given IV; Other Names: 177Lu-labeled PSMA-617; 177Lu-PSMA-617; Pluvicto; Lu177-PSMA-617; Lutetium-177-PSMA-617; AAA 617; AAA-617; AAA617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN
Experimental: Arm II (177Lu-PSMA-617 treatment pause); 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. Patients may resume treatment with 77Lu-PSMA-617. 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.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Single Photon Emission Computed Tomography; Undergo SPECT/CT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Other: Gallium Ga 68 Gozetotide; Given IV; Other Names: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC; (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68Ga)Glu-urea-Lys(Ahx)-HBED-CC; 68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-PSMA; 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; 68Ga-PSMA; 68Ga-PSMA-11; 68Ga-PSMA-HBED-CC; [68Ga] Prostate-specific Membrane Antigen 11; [68Ga]GaPSMA-11; Ga PSMA; Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled PSMA-11; GA-68 PSMA-11; Gallium Ga 68 PSMA-11; Gallium Ga 68-labeled PSMA-11; GALLIUM GA-68 GOZETOTIDE; Gallium-68 PSMA; Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; GaPSMA; PSMA-HBED-CC GA-68; AAA 517; AAA-517; AAA517; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Computed Tomography; Undergo SPECT/CT or PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Given IV; Other Names: 177Lu-labeled PSMA-617; 177Lu-PSMA-617; Pluvicto; Lu177-PSMA-617; Lutetium-177-PSMA-617; AAA 617; AAA-617; AAA617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN; Other: Clinical Observation; Undergo active monitoring; Other Names: observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	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.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to subsequent treatment (TTST)	TTST is defined as the time from randomization to subsequent treatment.	Up to 5 years
Time to progression (TTP)	TTP is defined as the time from randomization to disease progression.	Up to 5 years
Overall survival	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.	Up to 5 years
Incidence of adverse events	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.	Up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Matthew P. Thorpe, M.D., Ph.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Edetic Acid; Gallium 68 PSMA-11; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; Pluvicto
• Other Study ID Numbers: MC231005 (Other Identifier: Mayo Clinic); 23-006547 (Other Identifier: Mayo Clinic Institutional Review Board); NCI-2023-10664 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); MI-BET (Other Identifier: Mayo Clinic)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No