Recruiting
Phase 1

177^Lu-PSMA-617 & Sipuleucel-T

Sponsor:

City of Hope Medical Center

Code:

NCT07219147

Conditions

Metastatic Castration-Resistant Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Scan

Computed Tomography

Leukapheresis

Lutetium Lu 177 Vipivotide Tetraxetan

Study Details

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.

Conditions

Metastatic Castration-Resistant Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Study ID

NCT07219147

Start date

Mar 6, 2026

Status verified date

Apr, 2026

Completion date

Jul 26, 2028

Anticipated

Primary completion date

Jul 26, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: 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.

experimental: 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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Bone Scan

Undergo bone scan

Computed Tomography

Undergo CT and PSMA PET/CT

Leukapheresis

Undergo leukapheresis

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

Magnetic Resonance Imaging

Undergo MRI

PSMA PET Scan

Undergo PSMA PET/CT

Sipuleucel-T

Given IV

Primary outcome measure

  • Anti-prostatic acid phosphatase (PAP) immunoglobulin G (IgG) antibody response rate [ Time Frame: Between week 7 and week 19 ]
  • Change in anti-PAP IgG antibody titers [ Time Frame: Between week 7 and week 19 ]

Central Contacts and Locations

Central contacts

Alexander Chehrazi-Raffle, MD

6263598111aChehraziraffle@coh.org

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Alex Chehrazi-Raffle, MD

626-283-3284achehraziraffle@coh.org

Principal Investigator:

Alex Chehrazi-Raffle

More Information

Sponsor

City of Hope Medical Center

Last update posted

Apr 20, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-04-20.