CAR-T Cells +/− Radiation for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Systemic steroids

Disqualifiers: Arrhythmia, Optic neuritis, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 cycles (each cycle is 56 days)

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for prostate cancer that continues to grow despite hormone-blocking treatments. It tests the safety and effects of a therapy using altered immune cells, called CAR T-cells (Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes), designed to target cancer cells. Some participants will also receive radiation to determine if it enhances the treatment's effectiveness. The trial seeks men whose prostate cancer has spread and persists despite treatments aimed at lowering testosterone levels. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using systemic steroids or chronic immunosuppressants. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PSCA-CAR T cells, a treatment where a patient's immune cells are modified to fight cancer, are generally well-tolerated. Previous studies found that while these treatments can cause side effects, they are usually manageable. Common reactions include fever, tiredness, and low blood counts, which are temporary and treatable.

Adding radiation to PSCA-CAR T cells might enhance the treatment's effectiveness, but it can also cause additional side effects like skin irritation or tiredness. Data from earlier trials suggest that most patients can handle these combined treatments without serious problems.

As this is an early-phase trial, the main goal is to understand safety and determine the best dose. While past studies provide some evidence of safety, more research is needed to fully understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for prostate cancer, which often rely on hormone therapy, surgery, or chemotherapy, this new approach uses CAR-T cells that are engineered to specifically target and destroy cancer cells expressing the PSCA protein. Researchers are excited because these CAR-T cells have a unique mechanism of action by redirecting the body's own immune system to attack cancer cells with high precision. Additionally, one treatment plan combines these CAR-T cells with radiation, potentially enhancing their effectiveness by further weakening the cancer cells and making them more susceptible to immune attack. This targeted and personalized approach offers hope for better outcomes with potentially fewer side effects than traditional treatments.

What evidence suggests that this trial's treatments could be effective for castration-resistant prostate cancer?

Research has shown that PSCA-CAR T cells, a treatment in this trial, might help treat castration-resistant prostate cancer by more effectively targeting cancer cells. Early studies have demonstrated that these specially designed T cells can attack prostate cancer cells that have spread in the body. Another treatment arm in this trial combines PSCA-CAR T-cell therapy with radiation therapy, which uses high-energy x-rays to kill cancer cells. Combining CAR T-cell therapy with radiation may destroy more cancer cells. Although more research is needed, these findings suggest a promising direction for treating this challenging type of prostate cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Tanya Dorff, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for men aged 18+ with metastatic castration-resistant prostate cancer that has spread and shows PSCA protein presence. They must have adequate organ function, no severe allergies to study agents, no active infections or bleeding disorders, not be HIV or hepatitis B/C positive, and agree to birth control measures.

Inclusion Criteria

Corrected QT interval (QTc) =< 480 ms

My prostate cancer is resistant to hormonal therapy.

Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV), and syphilis

Exclusion Criteria

I have not had a stroke or brain bleed in the last 6 months.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

I have a history of optic neuritis or other immune-related brain diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Lymphodepletion

Patients undergo leukapheresis and lymphodepletion as preparation for CAR T-cell therapy

1-2 weeks

Treatment

Patients receive PSCA-CAR T cells intravenously up to 3 times, with or without radiation therapy

Up to 3 cycles (each cycle is 56 days)

Follow-up

Participants are monitored for safety, effectiveness, and disease response after treatment

Up to 1 year

Long-term Follow-up

Participants are monitored for long-term safety and survival outcomes

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes
• External Beam Radiation Therapy

Trial Overview The trial tests the safety and optimal dose of modified immune cells (PSCA-CAR T-cells) designed to target prostate cancer cells, given with or without radiation therapy. It aims to see if these treatments can better eliminate tumors in patients whose prostate cancer continues growing despite hormone therapy.

How Is the Trial Designed?

Group I: Treatment plan II (PSCA CAR T-cells, radiation) Experimental Treatment 8 Interventions

Patients undergo leukapheresis, radiation in 2 doses, and lymphodepletion, and receive PSCA-CAR T cells IV up to 3 times on study. Patients undergo bone scan, CT scan, tumor biopsy, and collection of blood, stool, and urine samples throughout the trial.

Group II: Treatment plan I (PSCA CAR T-cells) Experimental Treatment 7 Interventions

Patients undergo leukapheresis and lymphodepletion and receive PSCA-CAR T cells IV up to 3 times on study. Patients undergo bone scan, CT scan, tumor biopsy, and collection of blood, stool, and urine samples throughout the trial.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study found that using a 4-1BB co-stimulatory signaling domain in CAR T cells targeting prostate cancer leads to better selectivity for tumor cells with high antigen density and reduces T cell exhaustion, compared to the CD28 domain.

In patient-derived models of bone-metastatic prostate cancer, 4-1BB-containing CAR T cells showed superior persistence and effectiveness in controlling the disease, highlighting the importance of co-stimulation in CAR T cell therapy for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer. Priceman, SJ., Gerdts, EA., Tilakawardane, D., et al.[2021]

A novel T-cell engineering strategy allows T cells to target tumors by using a combination of a chimeric antigen receptor (CAR) and a chimeric costimulatory receptor (CCR), enabling them to specifically attack tumors expressing both targeted antigens, PSMA and PSCA.

This approach minimizes damage to healthy tissues by ensuring that T cells only activate and destroy tumors that express both antigens, potentially reducing side effects associated with traditional T-cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Kloss, CC., Condomines, M., Cartellieri, M., et al.[2021]

The study developed a third-generation CAR T cell targeting the prostate stem cell antigen (PSCA), which showed specific immune responses and effective tumor cell killing in laboratory tests.

In mouse models, treatment with PSCA-CAR T cells significantly delayed tumor growth and improved survival, suggesting potential for this therapy in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. Hillerdal, V., Ramachandran, M., Leja, J., et al.[2021]

CAR-T cell therapy has shown significant advancements in treating blood cancers like lymphoma and leukemia due to its high specificity and targeting capabilities, which differ from traditional T cell therapies.

Despite these successes, the application of CAR-T technology in treating solid tumors, such as prostate cancer, still faces many challenges, highlighting the need for further research and development in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CART cell therapy for prostate cancer: status and promise. Yu, H., Pan, J., Guo, Z., et al.[2020]

A new chimeric T-cell receptor (TCR) targeting the prostate stem cell antigen (PSCA) was successfully developed, showing promise for treating prostate cancer by activating cytotoxic T-cells against PSCA-positive tumor cells.

This innovative approach involves genetic engineering of T-cells to enhance their ability to recognize and attack prostate cancer cells, potentially offering a new immunotherapeutic strategy for patients with minimal residual disease or advanced tumor stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells. Morgenroth, A., Cartellieri, M., Schmitz, M., et al.[2021]

The study demonstrates that PSMA-targeting CAR T cells, which are engineered to include a dominant-negative TGFβ receptor, are safe and feasible for use in treating prostate cancer.

This approach suggests a promising strategy for enhancing the effectiveness of CAR T cell therapy in prostate cancer patients, potentially improving their treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells with a Dominant-Negative TGFβ Receptor Are Safe and Feasible. [2022]

A third-generation Chimeric Antigen Receptor (CAR) targeting Prostate Specific Membrane Antigen (PSMA) was developed to enhance the efficacy of CAR-T cell therapy for metastatic prostate cancer, but it showed similar in vitro antitumor activity to a second-generation CAR with only one costimulatory domain.

The addition of a second costimulatory domain in the third-generation CAR led to increased activation-induced cell death and an exhausted phenotype in CAR-T cells, suggesting that more costimulatory signals may not always improve treatment outcomes and should be carefully evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-Specific CAR-Engineered T Cells for Prostate Cancer: CD28 Outperforms Combined CD28-4-1BB "Super-Stimulation". Zuccolotto, G., Penna, A., Fracasso, G., et al.[2021]

Engineering NK-92 cells with a CAR that targets the prostate-specific membrane antigen (PSMA) allows these cells to effectively kill prostate cancer cells while sparing healthy cells, demonstrating strong potential for targeted therapy.

In mouse models, irradiated NK-92/CAR cells not only inhibited tumor growth but also improved survival rates, suggesting that this approach could be a promising and safe immunotherapy for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer. Montagner, IM., Penna, A., Fracasso, G., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05805371

NCT05805371 | PSCA-Targeting CAR-T Cells Plus or ... Giving PSCA-targeting CAR T-cells, with or without radiation, may kill more tumor cells in men with castration-resistant prostate cancer. Detailed Description.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02186

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for ... This phase Ib trial tests the safety, side effects, and best dose of autologous anti-prostate stem cell antigen (PSCA)-chimeric antigen receptor ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38867077/

PSCA-CAR T cell therapy in metastatic castration-resistant ... We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03873805?tab=results

Study Results | NCT03873805 | PSCA-CAR T Cells in ... Biological : Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes; Drug : Cyclophosphamide; Drug : Fludarabine; Drug : Fludarabine Phosphate.

5. clinicaltrial.be clinicaltrial.be/en/details/64766?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

PSCA-CAR T Cells in Treating Patients With PSCA+ ... Define the safety and tolerability of autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes (PSCA-CAR T cells) in patients with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8833489/

Chimeric Antigen Receptor T-Cell Therapy in Metastatic ... This review focuses on the role of chimeric antigen receptor T-cell therapy (CAR-T) in men with metastatic castrate-resistant prostate cancer.