Poly-ICLC for Prostate Cancer

Overseen By Cristina Pasat-karasik, RN

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Ashutosh Kumar Tewari

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Neuroendocrine tumors, Advanced disease, 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: 19

114 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a treatment called Poly-ICLC on prostate cancer in men undergoing active surveillance, meaning their cancer is closely monitored but not actively treated. The goal is to determine if Poly-ICLC, administered through injections into the muscle and directly into the tumor, can affect the cancer compared to no treatment. Men diagnosed with early-stage prostate cancer (specifically ISUP Grade 1 or 2) who have not undergone surgery or radiation might be suitable candidates. This trial may help identify new ways to manage prostate cancer without immediate surgery or radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in prostate cancer management.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on immunosuppressive medications or systemic corticosteroids. If you are taking oral 5-alpha-reductase inhibitors, you must stop them at least 6 months before joining the study.

Is there any evidence suggesting that Poly-ICLC is likely to be safe for humans?

Research shows that Poly-ICLC, also known as Hiltonol®, is generally safe for treating prostate cancer. Earlier studies found that patients tolerate this treatment well, as it helps the immune system fight cancer cells. Safety data from past research indicate that Poly-ICLC can be administered without causing major side effects, suggesting it doesn't pose significant risks. However, like any treatment, some minor side effects might occur. These findings reassure potential participants about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard treatments for prostate cancer, like hormone therapy or chemotherapy, Poly-ICLC (Hiltonol®) introduces a unique approach by using an active ingredient called polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose. This compound is known to activate the immune system, potentially enhancing the body's ability to fight cancer cells. Additionally, its administration method, involving both intramuscular and intertumoral injections, allows for targeted delivery right where it's needed most. Researchers are excited because this method might lead to improved outcomes by boosting the immune response directly at the tumor site.

What evidence suggests that Poly-ICLC might be an effective treatment for prostate cancer?

Research shows that Poly-ICLC (Hiltonol®), which participants in this trial may receive, might help the immune system fight prostate cancer. Studies have found that this treatment can safely alter the tumor environment to enhance the body's natural defenses against cancer. In one study, all patients tolerated the treatment well and did not need to stop due to side effects. Although researchers are still gathering long-term data, these early results are promising for its potential to effectively treat prostate cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Dimple Chakravarty, PhD

Principal Investigator

Assistant Professor

Sujit S Nair, PhD

Principal Investigator

Assistant Professor and Director of GU Immunotherapy Research

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer who are being closely monitored (active surveillance) instead of immediate treatment. Specific eligibility details aren't provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

I haven't had uncontrolled heart issues or a heart attack in the last 6 months.

Written informed consent and HIPAA authorization for release of personal health information

No clinically significant infections as judged by the treating investigator

Exclusion Criteria

I have a neuroendocrine tumor.

My cancer has spread to nearby tissues or lymph nodes.

I have been diagnosed with another type of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconditioning

Paired IM Poly-ICLC, 1.5 mg to reduce tumor induced suppression

1 week

1 visit (in-person)

Immune Priming

Intratumor Poly-ICLC 1.0 mg once

1 week

1 visit (in-person)

Boosting

Paired 1.5 mg IM Poly-ICLC weekly

8 weeks

8 visits (in-person)

Maintenance

Paired IM Poly-ICLC once a month

9 months

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Poly-ICLC

Trial Overview The study is testing Hiltonol® (Poly-ICLC), which will be given as shots into a muscle or directly into the tumor. It's a phase II pilot study to see if this treatment can benefit those on active surveillance compared to no treatment at all.

How Is the Trial Designed?

Group I: Control (Standard of Care) Active Control 1 Intervention

Group II: Hiltonol (Poly-ICLC) Active Control 2 Interventions

Enrolled study subjects will receive paired intramuscular (IM) and intertumoral. (IT) injections of the drug Poly-ICLC (Hiltonol®) as follows: Paired 1.5 mg IM (week 1), 1 mg IT once (week 2), followed by paired 1.5 mg IM weekly from weeks 3-through10, and at weeks 14, 18, 22, 26, 30, 34, 38, 42 and 46 with a 4-week rest period between IM injections.

Who Is Running the Clinical Trial?

Ashutosh Kumar Tewari

Lead Sponsor

Trials

3

Recruited

150+

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Published Research Related to This Trial

In a phase II study involving 30 adults with glioblastoma, the combination of poly-ICLC and radiation therapy resulted in a 1-year survival rate of 69% and a median survival of 65 weeks, indicating a potential survival advantage over historical data without chemotherapy.

The treatment was relatively well-tolerated, but did not show a survival benefit compared to radiation therapy combined with other chemotherapy agents, suggesting that further research is needed to explore poly-ICLC's effectiveness in combination with standard treatments like temozolomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01-05). Butowski, N., Chang, SM., Junck, L., et al.[2022]

In a pilot study involving patients with recurrent metastatic head and neck squamous cell cancer and melanoma, poly-ICLC was well tolerated and showed promising immune responses, with one patient achieving stable disease for 6 months after treatment.

The treatment led to significant changes in immune markers, such as increased levels of CD4, CD8, PD1, and PD-L1 in the tumor of the patient who benefited, indicating that poly-ICLC may effectively activate the immune system against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial. Kyi, C., Roudko, V., Sabado, R., et al.[2022]

Polyinosinic:polycytidylic acid (poly-ICLC) has shown potential as an effective adjuvant in cancer vaccines, enhancing anti-tumor immune responses and aiding in tumor elimination in both animal models and human patients.

Current research is actively exploring poly-ICLC-containing cancer vaccines in ongoing clinical trials, suggesting it may play a significant role in future cancer immunotherapy approvals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. Ammi, R., De Waele, J., Willemen, Y., et al.[2022]

In a study involving tumor-bearing mice, the optimal therapeutic dose of poly(I,C)-LC (100 micrograms twice a week) not only enhanced immune response but also correlated with improved survival rates, indicating its efficacy in treating tumor ascites.

The study found that this optimal dosing schedule was less toxic compared to the maximum tolerated dose (50 micrograms daily), suggesting a safer approach to immunomodulation in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dissociation of therapeutic and toxic effects of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose in tumor-bearing mice. Hartmann, D., Adams, JS., Meeker, AK., et al.[2020]

The administration of poly(I,C)-LC, a nontoxic immunotherapy, effectively eradicated established pulmonary metastases in experimental models, requiring 3 to 5 injections per week for at least 4 weeks for optimal results.

When combined with chemotherapy, poly(I,C)-LC improved survival rates in patients with high tumor burdens, suggesting it could serve as a valuable adjuvant treatment for cancer metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose. Talmadge, JE., Adams, J., Phillips, H., et al.[2021]

Poly-ICLC enhances T cell responsiveness and significantly boosts the delayed type hypersensitivity response in mice, indicating its role as a T cell stimulator.

The treatment also markedly increases the tumoricidal activity of macrophages and natural killer cells, with effects lasting over 3 days, likely due to sustained high levels of interferon in the serum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune response modifying activity in mice of polyinosinic: polycytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly-ICLC]. Chirigos, MA., Papademetriou, V., Bartocci, A., et al.[2020]

In Phase I trials involving 32 patients with advanced cancer, the synthetic polyribonucleotide complex poly(I,C)-LC was found to effectively induce interferon (IFN) in most patients, achieving serum levels comparable to intramuscular IFN-alpha administration.

Despite its efficacy in inducing IFN, the treatment was associated with significant toxicity, including fever and hypotension, which limits its use in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trials of poly(I,C) complexes in advanced cancer. Krown, SE., Kerr, D., Stewart, WE., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06343077

NCT06343077 | Intratumoral and Systemic Hiltonol® (Poly- ... This is a partially blinded randomized controlled phase II pilot study comparing Poly-ICLC (Hiltonol®) treatment vs no treatment, for prostate ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S266663402500306X

Article Prostate cancer in situ autovaccination with the ... Conclusions. Intratumoral poly-ICLC immunotherapy for PCa is safe and may modulate the tumor microenvironment, enhancing antitumor responses. ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41173002/

Modulating the cold tumor microenvironment Findings: All patients tolerated poly-ICLC without dose-limiting toxicity or treatment withdrawal. Median follow-up was 4.5 years. Seventy ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03262103

Neoadjuvant Hiltonol® (PolyICLC) for Prostate Cancer The purpose of this study is to test an approach of stimulating the body's immune system to attack prostate cancer. This study will test injection of a ...

5. trialx.com trialx.com/clinical-trials/listings/287697/intratumoral-and-systemic-hiltonol-poly-iclc-in-prostate-cancer-patients-on-active-surveillance/

Intratumoral and Systemic Hiltonol® (Poly-ICLC) in ... This is a partially blinded randomized controlled phase II pilot study comparing Poly-ICLC (Hiltonol®) treatment vs no treatment, for prostate ...