Sipuleucel-T + BAT for Prostate Cancer

Overseen By Laura Kane

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for men with metastatic castration-resistant prostate cancer, a type that has spread and does not respond to hormone therapy. The researchers aim to evaluate how well the combination of Sipuleucel-T (a cancer vaccine) and bipolar androgen therapy (BAT) enhances the immune response against cancer. Participants will receive regular testosterone injections (Testosterone Cypionate) along with Sipuleucel-T infusions. Men whose prostate cancer has spread, does not respond to hormone treatments, and who experience minimal symptoms might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in prostate cancer therapy.

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.

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

Research shows that Sipuleucel-T is generally easy for patients to handle. Studies have found it safe for individuals with advanced prostate cancer that no longer responds to hormone therapy. Most people experience only mild side effects, such as fever and chills, which are common with treatments that boost the immune system to fight cancer.

The FDA has already approved Sipuleucel-T, supporting its safety. Additionally, real-world evidence confirms its safety, showing consistent results in patients.

Testosterone cypionate is often used in treatments and is generally safe. Some people might experience side effects like mood changes or an increase in red blood cells, but these are usually manageable.

Overall, using these treatments together appears well-tolerated, with mostly mild to moderate side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sipuleucel-T combined with testosterone cypionate for prostate cancer because it offers a novel approach to treatment. Most standard therapies for prostate cancer, like hormone therapies and chemotherapy, focus on lowering testosterone levels or directly attacking cancer cells. However, this combination uses testosterone cypionate to potentially enhance the immune response generated by Sipuleucel-T, an immunotherapy designed to stimulate the body's own immune system to fight the cancer. This unique strategy of boosting immune function with hormone therapy could lead to improved outcomes for patients.

What evidence suggests that Sipuleucel-T + BAT could be effective for prostate cancer?

Research has shown that Sipuleucel-T can reduce the risk of death in men with advanced prostate cancer that no longer responds to hormone therapy. Sipuleucel-T uses the body's immune system to fight cancer. Studies have confirmed that it can extend patients' lives. In this trial, participants will receive a combination of Sipuleucel-T and bipolar androgen therapy (BAT), which uses testosterone to enhance the body's response. Early results suggest this combination might improve the immune system's reaction. Sipuleucel-T and BAT target cancer in different ways, potentially leading to better outcomes for patients. ^{1 3 4 5 6}

Who Is on the Research Team?

Joseph W. Kim, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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]

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 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 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 (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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06100705

Sipuleucel-T Combined with Bipolar Androgen Therapy in ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3460263/

Sipuleucel-T: harbinger of a new age of therapeutics for ... Sipuleucel-T (Provenge) is the first therapeutic cancer vaccine approved by the US FDA. The approval heralds the long-awaited promise of improved patient ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1001294

Sipuleucel-T Immunotherapy for Castration-Resistant ... Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration- ...

4. researchgate.net researchgate.net/publication/359600915_Real-World_Effectiveness_of_Sipuleucel-T_on_Overall_Survival_in_Men_with_Advanced_Prostate_Cancer_Treated_with_Androgen_Receptor-Targeting_Agents

(PDF) Real-World Effectiveness of Sipuleucel-T on Overall ... Abstract and Figures. Introduction: The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) continues to evolve.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-00050

Bipolar Androgen Therapy in Combination with Sipuleucel ... Sipuleucel-T is a form of immunotherapy approved for the treatment of metastatic castration-resistant prostate cancer. It is made from immune system cells ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6856402/

Real‐world outcomes of sipuleucel‐T treatment in PROCEED ... The safety and tolerability of sipuleucel‐T in PROCEED were consistent with previous findings. Keywords: immunotherapy, overall survival, prostate cancer, ...