Sipuleucel-T + BAT for Prostate Cancer

Overseen By Julie Holub

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Androgen inhibitors, Chemotherapy, Immunotherapy, others

Disqualifiers: Hepatic metastases, Active infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, single-arm phase II study of bipolar androgen therapy (BAT) given in addition with standard of care Sipuleucel-T to determine the interferon (IFN) gamma Enzyme-linked Immunospot (ELISPOT) response rate to PA2024 (an engineered fusion protein of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor which the activated autologous dendritic cells in the Sipuleucel-T vaccine are loaded with) in patients with metastatic castration resistant prostate cancer (mCRPC).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like androgen/AR signaling inhibitors, chemotherapy for mCRPC, and some other therapies must not have been used recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Sipuleucel-T for prostate cancer?

Research shows that Sipuleucel-T, an immunotherapy, improves overall survival in men with advanced prostate cancer, specifically those with metastatic castration-resistant prostate cancer. Clinical trials demonstrated a significant survival advantage, with a 4.1-month improvement in median survival compared to placebo. ^{1 2 3 4 5}

Is Sipuleucel-T safe for humans?

Sipuleucel-T has been tested in several clinical trials for prostate cancer, and common side effects include mild to moderate muscle pain, chills, fever, and tremor, which usually go away quickly. ^{1 4 6 7 8}

How is the treatment Sipuleucel-T + BAT unique for prostate cancer?

Sipuleucel-T is a unique treatment for prostate cancer because it uses the patient's own immune cells to fight the cancer, which is different from traditional treatments like chemotherapy. It involves collecting immune cells from the patient, treating them to target prostate cancer, and then reintroducing them into the body to stimulate an immune response. This approach has shown to improve survival in patients with advanced prostate cancer. ^{1 2 3 4 9}

Research Team

Joseph W. Kim, MD

Principal Investigator

Yale University

Eligibility Criteria

Men with metastatic castration-resistant prostate cancer (mCRPC) who have not been treated with more than two androgen/AR signaling inhibitors, no prior chemotherapy for mCRPC within the last year, or recent systemic anti-cancer therapy. Participants must be in good health otherwise, with proper liver and kidney function, a low PSA level (<20ng/dL), and an ECOG Performance Status of 0 or 1.

Inclusion Criteria

Your bilirubin level is below 2.0 times the UNL.

My PSA levels have risen twice, each time by at least 50% and are over 1.0 ng/mL.

Your serum creatinine is below 2.0x the upper normal limit.

Exclusion Criteria

Radiographic evidence of hepatic metastases

I have received Sipuleucel-T or high-dose testosterone for prostate cancer.

I have been treated with 3 or more prostate cancer drugs like abiraterone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive testosterone injections every 4 weeks and Sipuleucel-T infusions every 2 weeks for a total of 3 infusions

12 weeks

3 visits (in-person) for Sipuleucel-T infusions, additional visits for testosterone injections

Follow-up

Participants are monitored for safety, immune response, and clinical outcomes

12 months

Regular assessments every 4 weeks, radiographic assessments every 12 weeks

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

Treatment Details

Interventions

• Sipuleucel-T
• Testosterone Cypionate

Trial Overview This phase II trial is testing the combination of Sipuleucel-T (a prostate cancer vaccine) with bipolar androgen therapy (BAT), using Testosterone Cypionate to see if it can boost immune response against prostate cancer cells in men whose disease has resisted standard hormonal treatments.

Participant Groups

Group I: Testosterone Cypionate + Sipuleucel-T Experimental Treatment 2 Interventions

Participants will start with testosterone injection every 4 weeks. The first dose of standard of care Sipuleucel-T will be prepared and infused after two doses of testosterone and will continue every 2 weeks for a total of 3 infusions at a standard schedule. The testosterone injection will continue once every 4 weeks until treatment discontinuation criteria are met.

Sipuleucel-T is already approved in United States for the following indications:

Approved in United States as Provenge for:

• Asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Dendreon

Industry Sponsor

Trials

30

Recruited

5,200+

Findings from Research

Sipuleucel-T is an innovative immunotherapy that uses a patient's own dendritic cells to target prostate cancer, showing promising results in reducing prostate-specific antigen levels and extending the time before these levels double in men with biochemically relapsed prostate cancer.

In Phase III trials, sipuleucel-T significantly improved median overall survival in men with asymptomatic, metastatic hormone-refractory prostate cancer compared to placebo, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T (APC8015) for prostate cancer. So-Rosillo, R., Small, EJ.[2022]

Sipuleucel-T is an innovative immunotherapy that stimulates the immune system to fight against castration-resistant prostate cancer (CRPC) by using the patient's own dendritic cells modified with a specific protein.

A phase III trial showed that Sipuleucel-T significantly improved overall survival in patients with asymptomatic or minimally symptomatic CRPC, despite not affecting prostate-specific antigen levels or producing objective tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists. Garcia, JA.[2021]

Sipuleucel-T is an autologous cellular immunotherapy that effectively stimulates the immune system to target prostate cancer, leading to prolonged overall survival in men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC).

The findings from phase III studies highlight the efficacy and safety of sipuleucel-T, suggesting its important role in the treatment of advanced prostate cancer and indicating potential directions for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T for the treatment of advanced prostate cancer. Frohlich, MW.[2016]

Sipuleucel-T is an FDA-approved immunotherapy that effectively stimulates the patient's immune system to target metastatic castration-resistant prostate cancer, showing improved overall survival in three phase III clinical trials.

The treatment involves collecting the patient's immune cells, modifying them with a specific protein, and then reintroducing them to enhance the immune response against cancer, with future research suggesting potential for use in earlier stages of prostate cancer and in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building on sipuleucel-T for immunologic treatment of castration-resistant prostate cancer. Shore, ND., Mantz, CA., Dosoretz, DE., et al.[2022]

Sipuleucel-T (Provenge) has been shown to provide a significant survival benefit for men with metastatic castration-resistant prostate cancer, improving median survival by 4.1 months compared to placebo (25.8 vs 21.7 months) in a Phase III trial involving 512 patients.

The treatment has a favorable toxicity profile and manageable administration, making it a promising option to combine with other standard therapies for prostate cancer, potentially enhancing overall treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T for prostate cancer: the immunotherapy era has commenced. Buonerba, C., Ferro, M., Di Lorenzo, G.[2016]

Sipuleucel-T therapy for prostate cancer is generally safe, with most adverse events being mild to moderate and resolving within two days, including chills (53.1%) and pyrexia (31.3%).

There was no significant increase in serious adverse events or autoimmune complications compared to controls, indicating that sipuleucel-T can be administered safely in an outpatient setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. Hall, SJ., Klotz, L., Pantuck, AJ., et al.[2016]

In two clinical trials involving 225 men with advanced prostate cancer, sipuleucel-T treatment resulted in a 33% reduction in the risk of death compared to placebo, indicating a significant survival benefit.

The treatment was associated with mostly mild side effects, such as chills and headaches, suggesting that sipuleucel-T has a favorable risk-benefit profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Higano, CS., Schellhammer, PF., Small, EJ., et al.[2022]

Sipuleucel-T (Provenge) is an active immunotherapy that helps the immune system recognize and attack prostate cancer cells, showing a survival benefit in men with advanced androgen-independent prostate cancer, although further confirmation in larger trials is needed.

The most common side effects of sipuleucel-T include mild to moderate myalgia, chills, fever, and tremor, which typically resolve quickly, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T (Provenge): active cellular immunotherapy for advanced prostate cancer. McKarney, I.[2010]

Sipuleucel-T, an autologous cellular immunotherapy, showed a median time to biochemical failure of 18.0 months compared to 15.4 months for the control group, indicating a potential benefit, although the difference was not statistically significant (P = 0.737).

Patients receiving sipuleucel-T experienced a 48% increase in PSA doubling time after testosterone recovery, suggesting enhanced biological activity, and the treatment was generally well tolerated with common side effects including fatigue, chills, and fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of autologous cellular immunotherapy with sipuleucel-T in androgen-dependent prostate cancer. Beer, TM., Bernstein, GT., Corman, JM., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Sipuleucel-T (APC8015) for prostate cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Sipuleucel-T for the treatment of advanced prostate cancer. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Building on sipuleucel-T for immunologic treatment of castration-resistant prostate cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Sipuleucel-T for prostate cancer: the immunotherapy era has commenced. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

Sipuleucel-T (Provenge): active cellular immunotherapy for advanced prostate cancer. [2010]

9. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of autologous cellular immunotherapy with sipuleucel-T in androgen-dependent prostate cancer. [2020]