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

Trial Summary

What is the purpose of this trial?

This is a partially blinded randomized controlled phase II pilot study comparing Poly-ICLC (Hiltonol®) treatment vs no treatment, for prostate cancer participants on active surveillance.

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.

What data supports the effectiveness of the drug Poly-ICLC for prostate cancer?

Research shows that Poly-ICLC can enhance the immune system's ability to fight cancer by activating immune cells and has been effective in reducing tumors in animal models and some human cancers. It has shown promise in other cancers, suggesting potential benefits for prostate cancer as well. ^{1 2 3 4 5}

Is Poly-ICLC generally safe for humans?

Poly-ICLC has been generally well tolerated in clinical trials, with common side effects being fatigue and mild inflammation at the injection site. Some trials reported fever, chills, low blood pressure, and changes in blood counts, but these were manageable with adjusted dosing. ^{2 3 5 6 7}

How is the drug Poly-ICLC unique in treating prostate cancer?

Poly-ICLC is unique because it acts as an immune modulator, enhancing the body's immune response to fight cancer by activating immune cells like natural killer cells and macrophages. This drug is administered systemically and can be used in combination with other treatments, potentially improving outcomes where traditional therapies alone are insufficient. ^{1 2 3 5 6}

Research Team

Sujit S Nair, PhD

Principal Investigator

Assistant Professor and Director of GU Immunotherapy Research

Dimple Chakravarty, PhD

Principal Investigator

Assistant Professor

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: 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.

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

Who Is Running the Clinical Trial?

Ashutosh Kumar Tewari

Lead Sponsor

Trials

3

Recruited

150+

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Findings from Research

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]

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 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 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]

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]

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]

References

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

Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose. [2021]

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

Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. [2022]

3. United States 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). [2022]

4. United States 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. [2020]

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

Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Immune response modifying activity in mice of polyinosinic: polycytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly-ICLC]. [2020]

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

Phase I trials of poly(I,C) complexes in advanced cancer. [2020]