RECRUITING

Cell Therapy (STEAP1 CART) With Enzalutamide for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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) still 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 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 kill more tumor cells in patients with mCRPC.

Official Title

Phase 1/2 Dose-Escalation and Cohort Study of STEAP1 CART With Enzalutamide in Participants With mCRPC

Quick Facts

Study Start:2024-12-01

Study Completion:2027-03-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06236139

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Tissue confirmation of prostate adenocarcinoma and STEAP1 expression. Confirmation of diagnosis must be or have been performed by internal pathology review of archival material at Fred Hutch/ University of Washington Medical Center (UWMC). Tissue will be stained by IHC to confirm STEAP1 expression * Measurable disease by RECIST 1.1 criteria or bone only metastases with measurable PSA ( ≥ 1 ng/mL) * Must have progressed (at least 2 rising PSA levels with at least a 1-week interval and a minimum PSA of 1.0 ng/mL, progression per RECIST 1.1, or 2 or more new bone lesions by bone scan), after becoming castration-resistant * Have received, at any time, a CYP17 inhibitor or a second-generation antiandrogen therapy, and a taxane, or they must decline or be ineligible to receive these * Castrate levels of testosterone (\< 50 ng/dL) with or without the use of androgen deprivation therapy * 18 years or older at the time of enrollment * Capable of understanding and providing a written informed consent * Fertile male participants and their female partners must be willing to use an effective contraceptive method before, during, and for at least 4 months after the STEAP1 CART cell infusion * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Participants will be permitted to receive radiation therapy for palliative purposes throughout the study period, except during the 2-week period prior to undergoing leukapheresis * Serum creatinine =\< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance \> 50 mL/min as calculated using the Cockcroft-Gault formula and not dialysis dependent * Total bilirubin ≤ 1.5 x ULN. Participants with suspected Gilbert syndrome may be included if Total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN * ≤ grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on ambient air * If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in 1 second (FEVI) \>= 50% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) of \>= 40% of predicted will be eligible * Participants \>= 60 years of age are required to have left ventricular ejection fraction (LVEF) evaluation performed within 1 year prior to lymphodepletion chemotherapy. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician * Absolute neutrophil count (ANC) \> 1500 cells/ mm\^3 * Hemoglobin \> 9 g/dL * Platelets \> 100,000 per mm\^3	* Expecting to conceive or father children for the duration of the trial through 4 months after T cell infusion * Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by principal investigator (PI) * Corticosteroid therapy at a dose equivalent of \>15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable * Concurrent use of other investigational anti-cancer agents except for androgen deprivation therapy * Active uncontrolled infection: human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication * Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements * Untreated brain metastases: Participants with small asymptomatic brain metastases ( \< 1 cm) or those with brain metastases previously treated and controlled with surgery or radiotherapy will be considered for inclusion at discretion of principal investigator, so long as all other eligibility criteria are met * Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of \> 15 mg prednisone (or equivalent) per day, unless otherwise approved by PI * Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable * Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI * Known allergic reactions to any of the components of study treatments

Inclusion Criteria

Exclusion Criteria

* Tissue confirmation of prostate adenocarcinoma and STEAP1 expression. Confirmation of diagnosis must be or have been performed by internal pathology review of archival material at Fred Hutch/ University of Washington Medical Center (UWMC). Tissue will be stained by IHC to confirm STEAP1 expression
* Measurable disease by RECIST 1.1 criteria or bone only metastases with measurable PSA ( ≥ 1 ng/mL)
* Must have progressed (at least 2 rising PSA levels with at least a 1-week interval and a minimum PSA of 1.0 ng/mL, progression per RECIST 1.1, or 2 or more new bone lesions by bone scan), after becoming castration-resistant
* Have received, at any time, a CYP17 inhibitor or a second-generation antiandrogen therapy, and a taxane, or they must decline or be ineligible to receive these
* Castrate levels of testosterone (\< 50 ng/dL) with or without the use of androgen deprivation therapy
* 18 years or older at the time of enrollment
* Capable of understanding and providing a written informed consent
* Fertile male participants and their female partners must be willing to use an effective contraceptive method before, during, and for at least 4 months after the STEAP1 CART cell infusion
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants will be permitted to receive radiation therapy for palliative purposes throughout the study period, except during the 2-week period prior to undergoing leukapheresis
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance \> 50 mL/min as calculated using the Cockcroft-Gault formula and not dialysis dependent
* Total bilirubin ≤ 1.5 x ULN. Participants with suspected Gilbert syndrome may be included if Total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN
* ≤ grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on ambient air
* If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in 1 second (FEVI) \>= 50% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) of \>= 40% of predicted will be eligible
* Participants \>= 60 years of age are required to have left ventricular ejection fraction (LVEF) evaluation performed within 1 year prior to lymphodepletion chemotherapy. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician
* Absolute neutrophil count (ANC) \> 1500 cells/ mm\^3
* Hemoglobin \> 9 g/dL
* Platelets \> 100,000 per mm\^3

* Expecting to conceive or father children for the duration of the trial through 4 months after T cell infusion
* Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by principal investigator (PI)
* Corticosteroid therapy at a dose equivalent of \>15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable
* Concurrent use of other investigational anti-cancer agents except for androgen deprivation therapy
* Active uncontrolled infection: human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
* Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements
* Untreated brain metastases: Participants with small asymptomatic brain metastases ( \< 1 cm) or those with brain metastases previously treated and controlled with surgery or radiotherapy will be considered for inclusion at discretion of principal investigator, so long as all other eligibility criteria are met
* Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of \> 15 mg prednisone (or equivalent) per day, unless otherwise approved by PI
* Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable
* Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
* Known allergic reactions to any of the components of study treatments

Contacts and Locations

Study Contact

Fred Hutch Intake

CONTACT

206-606-1024

hutchdoc@fredhutch.org

Principal Investigator

Jessica Hawley

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

Jessica Hawley, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-01

Study Completion Date2027-03-30

Study Record Updates

Study Start Date2024-12-01

Study Completion Date2027-03-30

Terms related to this study

Additional Relevant MeSH Terms

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