Sipuleucel-T + Hormonal Therapy for Prostate Cancer

Overseen By Jingsong Zhang, MD, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: LHRH analog, NHA

Must not be taking: Chemotherapy, Radiotherapy

Disqualifiers: Brain metastases, Liver metastases, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat prostate cancer that has spread but remains asymptomatic, using the drug Sipuleucel-T (also known as Provenge, an immunotherapy). The study examines whether combining Sipuleucel-T with specific hormonal therapies, such as abiraterone or enzalutamide, can enhance treatment effectiveness by boosting the immune system. It is open to men with prostate cancer that has not worsened on scans but shows rising PSA levels and who are already on certain hormonal treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in prostate cancer therapies.

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 require that you are already on certain hormonal therapies for prostate cancer. If you are taking investigational drugs or have had recent chemotherapy or radiotherapy, you may need to stop those before joining the trial.

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

Research shows that sipuleucel-T, also known as Provenge, is generally easy for patients to handle. Previous studies found that it rarely causes serious side effects. After its market release, further analysis confirmed that while sipuleucel-T helps patients live longer, it usually doesn't lead to major health problems, suggesting the treatment is quite safe.

New hormonal agents (NHAs) like abiraterone, enzalutamide, and apalutamide are also commonly used and have been studied in many patients. They are generally well-tolerated, although some patients might experience side effects like tiredness or high blood pressure.

Both sipuleucel-T and NHAs have well-understood safety profiles, aiding in the management of any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Sipuleucel-T is unique because it is an immunotherapy that harnesses the body's own immune system to fight prostate cancer, unlike traditional treatments that typically involve surgery, radiation, or hormone therapy. What makes Sipuleucel-T stand out is its ability to stimulate an immune response specifically targeted against prostate cancer cells, offering a personalized approach to treatment. Researchers are excited about this treatment because it represents a shift towards more tailored cancer therapies, potentially offering improved outcomes for patients with fewer side effects compared to conventional methods.

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

Research shows that Sipuleucel-T, also known as Provenge, can extend the lives of men with advanced prostate cancer. Studies found that men treated with Sipuleucel-T had a 28% lower risk of dying compared to those who did not receive it. Additionally, nearly 38% more men who received Sipuleucel-T were alive three years after treatment compared to those who didn't. In this trial, participants will receive Sipuleucel-T either with or without new hormonal agents (NHA). When combined with new hormonal treatments, men tend to live even longer than with hormonal therapy alone. This suggests that Sipuleucel-T, especially when paired with other hormonal treatments, could be a promising option for improving survival in prostate cancer patients. ^{2 3 5 6 7}

Who Is on the Research Team?

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for men over 18 with metastatic prostate cancer that's not causing severe symptoms. They must be on hormone therapy and have a rising PSA level but no new cancer spread on scans. Participants need good organ function, controlled HIV if present, and can't have had recent chemotherapy or radiotherapy, prior Sipuleucel-T treatment, significant heart issues, or other serious illnesses.

Inclusion Criteria

I am a man who can father children and will use birth control during the study.

Ability to understand and the willingness to sign a written informed consent document

My heart functions well despite a history of heart issues.

Exclusion Criteria

I have cancer that has spread to my brain or liver.

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

You have taken an experimental medication within 30 days before starting treatment with Sipuleucel-T.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Sipuleucel-T with or without New Hormonal Agents (NHA) for the treatment of metastatic castration resistant prostate cancer

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including IgG responses and PSA progression

Up to 44 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Apalutamide
• Enzalutamide
• Sipuleucel-T

Trial Overview The study tests whether combining Sipuleucel-T (Provenge) with new hormonal agents like abiraterone, enzalutamide, or apalutamide improves immune system activation in men with advanced prostate cancer without visceral metastases. It aims to see if this combination can better target the cancer cells.

How Is the Trial Designed?

Group I: Sipuleucel-T without NHA Experimental Treatment 1 Intervention

Participants will discontinue use of New Hormonal Agents (NHA) while receiving sipuleucel-t as standard of care.

Group II: Sipuleucel-T with NHA Experimental Treatment 4 Interventions

Participants will continue taking New Hormonal Agents (NHA) while receiving sipuleucel-t as standard of care.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Dendreon

Industry Sponsor

Trials

30

Recruited

5,200+

Published Research Related to This Trial

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]

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, an autologous immunotherapy, significantly reduced the risk of death by 22% in men with metastatic castration-resistant prostate cancer, leading to a median survival increase of 4.1 months compared to placebo (25.8 months vs. 21.7 months).

While sipuleucel-T improved overall survival, it did not affect the time to disease progression, and common side effects included chills, fever, and headache, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T immunotherapy for castration-resistant prostate cancer. Kantoff, PW., Higano, CS., Shore, ND., et al.[2023]

Sipuleucel-T (Provenge) is the first FDA-approved therapeutic cancer vaccine, designed to enhance patient survival with minimal side effects by stimulating a specific immune response against cancer.

The development of sipuleucel-T has improved our understanding of patient populations and clinical trial endpoints for prostate cancer therapies, highlighting its significance in the evolution of cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T: harbinger of a new age of therapeutics for prostate cancer. Madan, RA., Gulley, JL.[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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9123060/

Real-World Effectiveness of Sipuleucel-T on Overall Survival ... This represents a 28% reduced risk of death with sipuleucel-T (hazard ratio 0.717 [95% CI 0.648, 0.793]; p < 0.01) based on a multivariate Cox ...

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

Sipuleucel-T Immunotherapy for Castration-Resistant ... The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to ...

3. provenge.com provenge.com/hcp/prolonged-survival/

Prolonged Survival | HCP Nearly 38% more men who received PROVENGE were still alive 3 years post treatment compared to control.1,b. b This information is data on file and represents an ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35352309/

Real-World Effectiveness of Sipuleucel-T on Overall ... This real-world study of mCRPC treatment indicates that men receiving sipuleucel T and an ARTA survive longer than men who only receive an ARTA, ...

5. aetna.com aetna.com/cpb/medical/data/800_899/0802.html

Sipuleucel-T (Provenge) - Medical Clinical Policy Bulletins In the integrated analysis of D9901 and D9902A, patients randomized to sipuleucel-T demonstrated a 33 % reduction in the risk of death (HR, 1.50; 95 % CI: 1.10 ...

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

Real‐world outcomes of sipuleucel‐T treatment in PROCEED ... Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2747749

Postmarketing Analysis of Sipuleucel-T Although an overall survival benefit was seen in clinical trials, sipuleucel-T treatment is rarely associated with significant changes in ...