Poly-ICLC for Prostate Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ashutosh Kumar Tewari
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Neuroendocrine tumors, Advanced disease, others
No Placebo Group
Prior Safety Data
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?
Is Poly-ICLC generally safe for humans?
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.12356
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
I am older than 18 years.
See 15 more
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.
See 3 more
Trial 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 (Virus Therapy)
Trial OverviewThe 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
2Treatment groups
Active Control
Group I: Hiltonol (Poly-ICLC)Active Control2 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 Control1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Icahn School of Medicine at Mount Sinai (ISMMS)New York, NY
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Who Is Running the Clinical Trial?
Ashutosh Kumar TewariLead Sponsor
Oncovir, Inc.Industry Sponsor
References
Immunotherapeutic potential in murine tumor models of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose. [2021]The systemic administration of multiple, nontoxic doses of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose [poly(I,C)-LC] eradicated established experimental and spontaneous pulmonary metastases. Optimal immunotherapy was schedule dependent, requiring three to five injections of poly(I,C)-LC per week for a minimum of 4 weeks; in addition, therapeutic efficiency was partially dosage independent. Immunotherapy by poly(I,C)-LC was found to be limited by tumor burden, although when combined with chemotherapy as a debulking regimen it resulted in increased survival with protocols in which poly(I,C)-LC alone was insufficient. These data suggest that the systemic administration of poly(I,C)-LC may provide a successful adjuvant therapeutic modality against cancer metastasis.
Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. [2022]Although cancer vaccination has yielded promising results in patients, the objective response rates are low. The right choice of adjuvant might improve the efficacy. Here, we review the biological rationale, as well as the preclinical and clinical results of polyinosinic:polycytidylic acid and its derivative poly-ICLC as cancer vaccine adjuvants. These synthetic immunological danger signals enhanced vaccine-induced anti-tumor immune responses and contributed to tumor elimination in animal tumor models and patients. Supported by these results, poly-ICLC-containing cancer vaccines are currently extensively studied in the ongoing trials, making it highly plausible that poly-ICLC will be part of the future approved cancer immunotherapies.
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]This phase II study was designed to determine the overall survival time of adults with supratentorial glioblastoma treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), in combination with and following radiation therapy (RT).
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]In this paper, we describe a study of the therapeutic parameters (dose and schedule) and immunomodulatory activity (macrophage, natural killer cell, and T-cell number and function) of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose [poly(I,C)-LC] in the treatment of MBL-2 tumor ascites. Tumor-bearing mice received an optimal therapeutic protocol [100 micrograms poly(I,C)-LC administered twice a wk], a maximum tolerated dose [50 micrograms poly(I,C)-LC administered daily], or the optimal immunomodulatory protocol for normal mice [10 micrograms poly(I,C)-LC administered daily]. The percentage of tumor-associated macrophages and their cytotoxic activity correlated with host survival. In addition, splenic T-cell activity correlated with host survival, and splenic natural killer cell function had a near significant correlation with host survival. These results indicate that the optimal dose and schedule of poly(I,C)-LC for immunomodulation in tumor-bearing animals are also the optimal therapeutic protocol but have less toxicity than the maximum tolerated dose.
Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial. [2022]Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells.Patients and Methods: In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and blood.Results: Two patients completed 2 cycles of IT treatments, and 1 achieved clinical benefit (stable disease, progression-free survival 6 months), whereas the remainder had progressive disease. Poly-ICLC was well tolerated, with principal side effects of fatigue and inflammation at injection site (<grade 2). In the patient with clinical benefit, IHC analysis of tumor showed increased CD4, CD8, PD1, and PD-L1 levels compared with patients with progressive disease. RNA-seq analysis of the same patient's tumor and peripheral blood mononuclear cells showed dramatic changes in response to poly-ICLC treatment, including upregulation of genes associated with chemokine activity, T-cell activation, and antigen presentation.Conclusions: Poly-ICLC was well tolerated in patients with solid cancer and generated local and systemic immune responses, as evident in the patient achieving clinical benefit. These results warrant further investigation and are currently being explored in a multicenter phase II clinical trial (NCT02423863). Clin Cancer Res; 24(20); 4937-48. ©2018 AACR.
Immune response modifying activity in mice of polyinosinic: polycytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly-ICLC]. [2020]Poly-ICLC, a polyinosinic: polycytidylic acid stabilized with poly-L-lysine in carboxymethyl-cellulose was tested in mice for its immunoregulatory activity. Poly-ICLC was found to enhance T cell responsiveness but not B cells. It augmented the delayed type hypersensitivity response significantly. The results indicate Poly-ICLC to be a T cell stimulator. Macrophage tumoricidal activity was markedly enhanced both in vitro and in vivo after exposure to Poly-ICLC. Natural killer cell cytotoxicity was significantly augmented in vivo. Both macrophage and natural killer cell activity was maintained for over 3 days after only one treatment. The extended period of tumor cell cytotoxicity, exhibited by macrophages and natural killer cells, may correlate to Poly-ICLC induction of early and high levels of interferon which are maintained in the serum for a longer period of time.
Phase I trials of poly(I,C) complexes in advanced cancer. [2020]We have performed Phase I trials of two synthetic double-stranded polyribonucleotide complexes--poly(I,C)-LC, a complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxymethylcellulose, and poly(I,C)-L, which lacks carboxymethylcellulose--in patients with advanced cancer. With poly(I,C)-LC, several treatment schedules were investigated in an attempt to decrease toxicity and maximize interferon (IFN) induction. The best tolerated was an alternate-day schedule, with gradual dose escalation. Daily short infusions and continuous (24-h) infusions were tolerated less well. Maximum tolerated doses varied over a several hundredfold dose range. Toxicity consisted of fever, rigors, hypotension, and blood count depression. Two patients treated with poly(I,C)-L developed systemic allergic reactions, and antibodies to poly(I,C)-L and its components were detected in the serum of some patients treated with both compounds. IFN-alpha was induced in most patients at serum levels similar to those achieved after intramuscular administration of human IFN-alpha. Of 32 patients, one with renal cell carcinoma showed partial tumor regression. Poly(I,C) complexes are effective IFN inducers in humans, but their toxicity limits their use in cancer patients.