48 Participants Needed

Cell Therapy + Enzalutamide for Prostate Cancer

FH
Overseen ByFred Hutch Intake
Age: 18+
Sex: Male
Trial Phase: Phase 1 & 2
Sponsor: Fred Hutchinson Cancer Center
Must be taking: Androgen inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use other investigational anti-cancer agents during the trial, except for androgen deprivation therapy.

What data supports the effectiveness of the treatment Cell Therapy + Enzalutamide for Prostate Cancer?

Research shows that targeting STEAP1 with CAR T cells can effectively attack prostate cancer cells, and enzalutamide has shown benefits in some prostate cancer patients. Combining these approaches may enhance the immune response against prostate cancer.12345

Is the combination of cell therapy and Enzalutamide safe for prostate cancer treatment?

The combination of Enzalutamide with other treatments, like Entinostat, has shown a promising safety profile in early studies for prostate cancer. Additionally, STEAP1-targeted CAR T cell therapies have demonstrated safety in preclinical models, suggesting they may be safe for further development in humans.12567

What makes the STEAP1 CART treatment for prostate cancer unique?

The STEAP1 CART treatment is unique because it involves using genetically modified immune cells (CAR T-cells) to specifically target and attack prostate cancer cells, which is different from traditional treatments like enzalutamide that focus on blocking androgen receptors to slow cancer growth.7891011

What is the purpose of this trial?

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.

Research Team

RN

Rosa Nadal Rios, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for men with metastatic castration-resistant prostate cancer, which has spread beyond the prostate and resists treatment to lower male hormones. Participants must have tried hormone therapy and chemotherapy without success.

Inclusion Criteria

My cancer can be measured by scans or I have cancer in the bones with a PSA level over 1.
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
My liver function tests, specifically AST and ALT, are within normal limits.
See 15 more

Exclusion Criteria

I am taking more than 15 mg of prednisone daily, but use it in short bursts for my condition.
I am not using any other experimental cancer treatments, except for hormone therapy to lower androgen levels.
My infections, including HIV or hepatitis, are well-controlled with medication.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Leukapheresis and Pre-treatment

Patients undergo leukapheresis and receive cyclophosphamide and fludarabine intravenously on days -5, -4, and -3

1 week
3 visits (in-person)

Treatment

Patients receive STEAP1 CART infusion on day 0 and may receive enzalutamide orally starting on day 0

Up to 1 year
Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years
Regular visits 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

Treatment Details

Interventions

  • Enzalutamide
  • STEAP1 CART
Trial Overview The trial tests STEAP1 CART cell therapy combined with enzalutamide, a drug blocking male hormones. It's checking if this combo can better target and kill prostate cancer cells that have spread and don't respond to usual treatments.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (STEAP1 CART, enzalutamide)Experimental Treatment13 Interventions
Patients undergo leukapheresis then receive cyclophosphamide IV and fludarabine IV on days -5, -4 and -3 and STEAP1 CART IV on day 0. Patients may receive enzalutamide PO on day 0 then QD in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy at baseline, day 14 and optionally at progression. Patients additionally undergo blood sample collection, NM bone scan and CT scan, or MRI or PET scan throughout study. Additionally, patients may undergo ECHO or MUGA at screening.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials
583
Recruited
1,341,000+

PromiCell Therapeutics, Inc.

Collaborator

Trials
1
Recruited
50+

Findings from Research

The study identified STEAP2 as a promising target for CAR-T therapy in prostate cancer due to its high expression on tumor cells and limited presence in normal tissues, reducing the risk of off-target effects.
The engineered CAR-T therapy, AZD0754, showed strong anti-tumor activity in both laboratory and mouse models, demonstrating its potential as a safe and effective treatment option for prostate cancer.
Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer.Zanvit, P., van Dyk, D., Fazenbaker, C., et al.[2023]
STEAP1 is a promising target for CAR T cell therapy in metastatic prostate cancer, showing effectiveness even at low antigen levels and demonstrating safety in preclinical models.
Combining STEAP1 CAR T cell therapy with a localized IL-12 treatment enhances the immune response against tumors, improving antitumor efficacy and addressing issues of treatment resistance due to STEAP1 antigen escape.
Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy.Bhatia, V., Kamat, NV., Pariva, TE., et al.[2023]
The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.
However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.
Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial.Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

References

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer. [2023]
Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy. [2023]
Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. [2023]
Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. [2022]
Development of STEAP1 targeting chimeric antigen receptor for adoptive cell therapy against cancer. [2022]
Phase I Study of Entinostat in Combination with Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. [2021]
Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model. [2021]
Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. [2021]
Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Enzalutamide for treatment of CRPC: rationale for sequencing and potential clinical biomarker for resistance. [2020]
Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. [2021]
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