177^Lu-PSMA-617 in Combination With Sipuleucel-T for the Treatment of Metastatic Castration-Resistant Prostate Cancer

NCT ID: NCT07219147

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-04
• Study Completion Date: 2027-06-28

Brief Summary

This phase I trial compares the effect of lutetium Lu 177 (177^Lu)-prostate-specific membrane antigen (PSMA)-617 in combination with Sipuleucel-T to 177^Lu-PSMA-617 alone in treating patients with prostate that has spread from where it first started (primary site) to other places in the body (metastatic) and has continued to grow and spread despite surgical or medical intervention to block androgen production (castration-resistant). 177^Lu-PSMA-617, a type of radioconjugate, binds to a protein called PSMA, which is found on some prostate tumor cells. It gives off radiation that may kill the tumor cells. Sipuleucel-T, a type of vaccine and a type of cellular adoptive immunotherapy, is made from immune system cells. The cells are treated with a protein that is made by combining a protein found on prostate tumor cells with a growth factor. When the cells are injected back into the patient, they may stimulate T cells to kill prostate tumor cells. Giving 177^Lu-PSMA-617 in combination with sipuleucel-T may be safe, tolerable, and/or effective compared to 177^Lu-PSMA-617 alone in treating patients with metastatic castration-resistant prostate cancer.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the immune response induced by the combination of lutetium Lu 177 vipivotide tetraxetan (177^Lu-PSMA-617) and sipuleucel-T, using changes in anti-prostatic acid phosphatase (PAP) immunoglobulin G (IgG) antibody titers.

SECONDARY OBJECTIVES:

I. To evaluate anti-PA2024 antibody titers in patients receiving 177^Lu-PSMA-617 alone versus in combination with sipuleucel-T.

II. To assess the safety and tolerability of 177^Lu-PSMA-617 plus sipuleucel-T. III. To evaluate the clinical efficacy of 177^Lu-PSMA-617 alone versus in combination with sipuleucel-T.

EXPLORATORY OBJECTIVES:

I. To characterize the pharmacokinetics (PK) of 177^Lu-PSMA-617 plus sipuleucel-T in the blood.

II. To determine the impact of 177^Lu-PSMA-617 in combination with sipuleucel-T on systemic immunomodulation.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A (CONTROL GROUP): Patients receive 177^Lu-PSMA-617 intravenously (IV). Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, PSMA positron emission tomography (PET)/computed tomography (CT), bone scan, and magnetic resonance imaging (MRI) throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

ARM B (EXPERIMENTAL GROUP): Patients receive 177^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting during week 8 of treatment, patients receive sipuleucel-T IV over 1 hour. Treatment repeat every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis, blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

After completion of study treatment, patients are followed up at 30 days, every 3 months for up to 1 year then every 6 months until progression followed by survival follow until death or withdrawal of consent.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (177^Lu-PSMA-617)

Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

Group Type: ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type: PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT and PSMA PET/CT

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type: DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

PSMA PET Scan

Intervention Type: PROCEDURE

Undergo PSMA PET/CT

Sipuleucel-T

Intervention Type: BIOLOGICAL

Given IV

Arm B (177^Lu-PSMA-617, sipuleucel-T)

Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting during week 8 of treatment, patients receive sipuleucel-T IV over 1 hour. Treatment repeat every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis, blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type: PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT and PSMA PET/CT

Leukapheresis

Intervention Type: PROCEDURE

Undergo leukapheresis

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type: DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

PSMA PET Scan

Intervention Type: PROCEDURE

Undergo PSMA PET/CT

Sipuleucel-T

Intervention Type: BIOLOGICAL

Given IV

Interventions

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT and PSMA PET/CT

Intervention Type: PROCEDURE

Leukapheresis

Undergo leukapheresis

Intervention Type: PROCEDURE

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

Intervention Type: DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

PSMA PET Scan

Undergo PSMA PET/CT

Intervention Type: PROCEDURE

Sipuleucel-T

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; Bone Scintigraphy; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; tomography; Leukocyte Adsorptive Apheresis; Leukocytopheresis; Therapeutic Leukopheresis; White Blood Cell Reduction Apheresis; 177Lu-labeled PSMA-617; 177Lu-PSMA-617; AAA 617; AAA-617; AAA617; Lu177-PSMA-617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN; Lutetium-177-PSMA-617; Pluvicto; Magnetic Resonance; Magnetic Resonance Imaging (MRI); Magnetic resonance imaging (procedure); Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI; MRI Scan; MRIs; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Structural MRI; Prostate-specific Membrane Antigen PET; PSMA PET; PSMA-Positron emission tomography; APC 8015; APC-8015; APC8015; APC8015 Vaccine; PA2024 (PAP/GM-CSF)-Loaded Dendritic Cell Vaccine; Provenge; SipT

Eligibility Criteria

Inclusion Criteria

• Documented informed consent of the participant and/or legally authorized representative

• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Male
• Progressive castration-resistant metastatic prostate cancer with pathologically confirmed adenocarcinoma of the prostate without small cell features
• Patients must have either:

• Measurable disease

• For extranodal (visceral) lesions (e.g. lung, liver, etc.) to be considered measurable, they must be ≥ 10 mm in one dimension, using spiral CT
• For lymph nodes to be considered measurable (i.e., target or evaluable lesions), they must be ≥ 20 mm in at least one dimension, using spiral CT
• OR non-measurable disease

• All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions
• Lesions that are considered non-measurable include bone lesions (only). Progression on first generation ADT
• Patients must have been on androgen deprivation therapy with a gonadotrophin releasing hormone (GnRH) analogue, antagonist, or bilateral orchiectomy (i.e., surgical or medical castration) for at least 3 months prior to study entry and maintain castrate levels of serum testosterone < 50 ng/dL throughout study participation unless intolerant
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3 (within 10 days prior to day 1 of protocol therapy)
• White blood cell (WBC) counts > 2500/uL (within 10 days prior to day 1 of protocol therapy)
• Lymphocyte count ≥ 300/uL (within 10 days prior to day 1 of protocol therapy)
• Platelets ≥ 100,000/mm^3 (within 10 days prior to day 1 of protocol therapy)
• Hemoglobin ≥ 9g/dL (within 10 days prior to day 1 of protocol therapy)

• NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 10 days prior to day 1 of protocol therapy) (unless has Gilbert's disease, serum bilirubin level ≤ 3 x ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (within 10 days prior to day 1 of protocol therapy)
• Alanine aminotransferase (ALT) ≤ 3.0 x ULN (within 10 days prior to day 1 of protocol therapy)
• Alkaline phosphatase ≤ 3 x ULN (within 10 days prior to day 1 of protocol therapy) (Patients with documented bone metastases, alkaline phosphatase [ALP] ≤ 5 x ULN)
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance of ≥ 50 mL/min per Cockcroft-Gault formula (within 10 days prior to day 1 of protocol therapy)
• If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN (within 10 days prior to day 1 of protocol therapy)
• If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (within 10 days prior to day 1 of protocol therapy)
• If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.3 x ULN (within 10 days prior to day 1 of protocol therapy)
• If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (within 10 days prior to day 1 of protocol therapy)
• Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) (within 10 days prior to day 1 of protocol therapy)

• If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed. OR
• If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
• Meets other institutional and federal requirements for infectious disease titer requirements

• Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
• For male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria

• Any approved or investigational anticancer therapy, including chemotherapy, hormonal therapy (e.g., androgen receptor [AR] antagonists, 5 alpha reductase inhibitor, estrogen), or radiotherapy, within 4 weeks prior to initiation of study treatment

• Treatment with any of the following medications or interventions within 28 days of registration:

• External beam radiation therapy or surgery
• Chrysanthemum morifolium/Ganoderma lucidum/Glycyrrhiza glabra/Isatis indigotica/Panax pseudoginseng/Rabdosia rubescens/Scutellaria baicalensis/Serona repens supplement (PC-SPES) (or PC-SPEC) or saw palmetto
• Systemic corticosteroids. Use of inhaled, intranasal, and topical steroids is acceptable
• Megestrol acetate (Megace®), diethyl stilbestrol (DES), or cyproterone acetate
• Ketoconazole
• 5-alpha-reductase inhibitors (e.g., finasteride [Proscar®], dutasteride [Avodart®])
• High dose calcitriol (1,25[OH]2 vitamin [Vit]D) (i.e., > 7.0 ug/week)
• Prior treatment with 177^Lu-PSMA-617 and/or sipuleucel-T
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Treatment with any investigational vaccine within 2 years of registration or treatment with any other investigational product within 28 days of registration
• Patients with acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
• Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
• Inability to comply with study and follow-up procedures
• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Chehrazi-Raffle

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

Facility Contacts

Alex Chehrazi-Raffle

Role: primary

achehraziraffle@coh.org

626-283-3284

Other Identifiers

NCI-2025-07470

Identifier Type: REGISTRY

Identifier Source: secondary_id

25161

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

25161

Identifier Type: -

Identifier Source: org_study_id