This phase I/II trial tests the safety and effectiveness of cell therapy (STEAP1 CART) with enzalutamide in treating patients with prostate cancer that continues to grow despite surgical or medical treatments to block androgen production (castration-resistant) and that has spread from where it first started (the prostate) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer deaths in men. Localized prostate cancer is often curable and even metastatic disease may respond to treatment for a few years. Despite multiple therapies, including hormone therapy and chemotherapy, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease. Recently, adoptive cellular immunotherapies have been developed to transfer immunogenic cells to the patient to produce an anti-tumor response. Chimeric antigen receptor T (CART)-cell therapy is a type of treatment in which a patient's T-cells (a type of immune cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Prostate stem cell antigen and prostate specific membrane antigen CAR T cell therapies have been shown to be safe and effective, but objective tumor responses remain rare. STEAP1 is an antigen that promotes cancer growth and spread and is found to be broadly expressed in mCRPC tissues. STEAP1 CART is composed of CAR T cells that have been engineered with a STEAP1 antigen to better target prostate tumor cells. Enzalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Giving STEAP1 CART with enzalutamide may be safe and/or effective in treating patients with mCRPC.
Additional locations may be listed on ClinicalTrials.gov for NCT06236139.
Locations matching your search criteria
United States
Washington
Seattle
Fred Hutch/University of Washington/Seattle Children's Cancer ConsortiumStatus: Active
Contact: Rosa M Nadal Rios
Phone: 206-606-6127
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of STEAP1 CART based on dose-limiting toxicities and evaluate the overall safety profile. (Phase I)
II. Confirm the safety and feasibility of RP2D STEAP1 CART in combination with enzalutamide. (Phase II)
SECONDARY OBJECTIVES:
I. To evaluate the anti-tumor effect of STEAP1 CART cell therapy alone (Part 1) and in combination with enzalutamide (Part 2) in treating participants with mCRPC.
II. To assess anti-tumor effect (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 and the Prostate Cancer Working Group 3 [PCWG3]) by treatment group and analyze clinical endpoints including prostate specific antigen (PSA) response, time to response, duration of response, radiographic progression free survival, overall survival.
EXPLORATORY OBJECTIVES:
I. Evaluate the persistence of transferred T cells in the blood and at the tumor site.
II. Evaluate the migration of infused transgenic T cells to tumor tissue.
III. Evaluate the phenotype of infused T cells that persist and localize to tumor.
IV. Evaluate the functional capacity of infused transgenic T cells.
V. Evaluate the presence or absence of epitope spreading (broadening of immune responses) in the peripheral blood and/or tumor microenvironment.
VI. Evaluate changes in the tumor tissue and microenvironment that may correlate with success and/or failure of the regimen.
VII. Evaluate the relationship between tumor STEAP1 expression by immunohistochemistry (IHC) and clinical response parameters.
VIII. Assess circulating biomarkers such as circulating tumor deoxyribonucleic acid (ctDNA), serum cytokines (IL-2, IFN-alpha, granulocyte-macrophage colony stimulating factor [GM-CSF]), and vector copy number (VCN) from participants’ blood over the course of CART treatment.
OUTLINE: This is a dose escalation study of STEAP1 CART followed by a dose expansion study in which STEAP 1 CART is used in combination with fixed-dose enzalutamide.
Patients undergo leukapheresis then receive cyclophosphamide intravenously (IV) and fludarabine IV on days -5, -4 and -3 and STEAP1 CART IV on day 0. In the dose expansion phase, patients also receive enzalutamide orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy at baseline, day 14 and optionally at progression. Patients additionally undergo blood sample collection, nuclear medicine (NM) bone scan and computed tomography (CT) scan, or magnetic resonance imaging (MRI) or positron emission tomography (PET) scan throughout study. Additionally, patients may undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening.
After completion of study treatment, patients are followed up at 2, 3, 4, 5, 6, 9, and 12 months then every 6 months up to year 5 followed by yearly up to year 15.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorRosa M Nadal Rios