Neoadjuvant Hiltonol® (PolyICLC) for Prostate Cancer

September 8, 2022 updated by: Ashutosh Kumar Tewari

Phase I Study of In Situ Autologous Vaccination Against Prostate Cancer With Intratumoral and Systemic Hiltonol® (Poly-ICLC) Prior To Radical Prostatectomy

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 substance polylysine and carboxymethylcellulose (Poly-ICLC, Hiltonol®)through a needle guided by MRI (magnetic resonance imaging) ultrasound fusion technology into the prostate gland. Poly ICLC has been used to help the body in its fight against cancer. The first aim of the study is to determine the highest dose of a substance Poly-ICLC (Hiltonol®) that can be safely tolerated by the study participants. The second aim of the study is to find out the toxicity or side effects of poly-ICLC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a pilot dose escalation study of IT/IM Poly-ICLC in patients with high risk clinically localized prostate cancer. The dose and frequency of IT injections will be increased in successive cohorts to define a safe dose and schedule for further testing.

Intratumoral + intramuscular poly-ICLC in patients with clinical localized prostate cancer. In the current pilot clinical trial, poly-ICLC will be administered intratumorally (Artemis guided) and intramuscularly (e.g., deltoid muscle) prior to prostatectomy in patients with clinically localized prostate cancer. Based on the available preclinical data exploring intratumoral administration of PAMPs described above, we expect this approach will result in three immunomodulatory steps26:

Immunomodulatory Step 1: Innate immune local tumor killing induced by intratumoral poly-ICLC - the initial intratumoral injections are expected to induce activation/recruitment of IL-12, TNF-α, and other cytokines and NK cells, resulting in early tumor killing and antigen release.9-11 Poly-ICLC may also have a direct antiproliferative effect on tumor cells mediated by interferon-inducible nuclear enzyme systems.

Immunomodulatory Step 2: Th1 and cytotoxic T lymphocyte priming as a result of the repeated in-situ poly-ICLC 'danger signal' combined with the tumor antigens released in step 1 and further processed and cross-presented by poly-ICLC-activated myeloid dendritic cells.7,8 Poly-ICLC is expected to recruit myeloid dendritic cells and macrophages to the tumor site where they can load with antigens being released through the innate mechanisms, present them Th1 cells, and cross-present them to CD8 T cells in the tumor or in the regional lymph nodes, thus generating antigen specific cytotoxic T lymphocytes.

Immunomodulatory Step 3 (or "Boost" phase): Maintenance of the systemic anti-tumor immune response and migration of cytotoxic T lymphocytes to remote metastases, through repeated intramuscular poly-ICLC induction of chemokines, other costimulatory factors, and inflammasome activation.23-25 The rationale for followup with intramuscular maintenance is that as part of the comprehensive response, dsRNAs such as poly-ICLC induce various chemokines and costimulatory factors that help target the response to tumor. For example, one of these costimulatory factors is OX40, which belongs to the tumor necrosis factor family of cytokines, and helps maintain cytotoxic lymphocyte longevity and action at the tumor and metastatic sites.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age > 18 years at the time of consent.
  • ECOG Performance Status of 0-1 within 14 days prior to being registered for protocol therapy (Study Procedure Manual).
  • Histologically confirmed adenocarcinoma of the prostate (with previous diagnostic tissue available for tumor marker analysis).
  • Gleason 7 - 10, cT2a - cT3b adenocarcinoma of the prostate with plans for radical prostatectomy
  • PSA ≥ 4 ng/ml
  • Tumor visible on multiparametric MRI
  • Tolerated previous transrectal ultrasound guided biopsy procedure under local anesthetic
  • Uncomplicated previous TRUS biopsy procedure (i.e., no prior hospitalization due to sepsis, prostatic abscess or severe hemorrhage following TRUS prostate biopsy)
  • Willing to undergo the intra-tumoral (IT) injection of the Poly-ICLC into the prostatic tumor as per the protocol
  • No prior hormonal therapy with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.). Patients who have received prior oral anti-androgen therapies (bicalutamide, flutamide, nilutamide, etc.) must be off treatment for at least 6 weeks prior to enrollment. Patients who have received prior LHRH agonist or antagonist therapy (leuprolide, goserelin acetate, etc.) are eligible provided serum testosterone is > 50 mg/dl.
  • No prior radiation therapy (external beam or brachytherapy) to the pelvis or prostate.
  • No clinically significant infections as judged by the treating investigator.

  • No characteristics suggesting a potential higher risk of infection with intraprostatic injections:

    • Recurrent urinary tract infections or history of prostatitis within 3 months prior to enrollment into the study.
    • Urine analysis positive for nitrites and leucocyte esterase. Such patients could be considered for the study after treatment and resolution of the infection.
    • Active proctitis
    • History of prostatic abscess
    • Taking immunosuppressive medication including systemic corticosteroids
    • Active hematologic malignancy
  • No uncontrolled angina, congestive heart failure or MI within 6 months.
  • Patients with history of HIV (if CD4+ T cell counts are ≥350 cells/µL on established ART therapy), Hepatitis B (with viral load below limits of quantification) or Hepatitis C (who have completed a curative therapy and have a viral load below the limit of quantification) are eligible for this study.

  • No treatment with any investigational agent for any medical condition within 28 days prior to being registered for protocol therapy.

    • Adequate end organ function as determined by the following laboratory values:

      • White blood cell count (WBC) > 2.5 k/mm3
      • Absolute neutrophil count (ANC) > 1.5 k/mm3
      • Hemoglobin (Hgb) > 8.0 g/dL
      • Platelets > 100 k/mm3
      • Calculated creatinine clearance of > 60 cc/min using the Cockcroft-Gault formula:

Males: (140 - Age in years) × Actual Body Weight in kg 72 × Serum Creatinine (mg/dL)

  • Bilirubin < 2.0 x ULN
  • Aspartate aminotransferase (AST) < 2.5 x ULN
  • Alanine aminotransferase (ALT) < 2.5 x ULN 18) Able to speak, read and write in English.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cohort 1
Intratumoral (IT) Poly ICLC 0.5 mg IT once/week (week 1) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intratumoral (IT) Poly ICLC 0.5 mg
0.5 mg IT once/week (week 1)
Biological: Intramuscular (IM) Poly ICLC
1 mg IM twice weekly (weeks 3-6)
Other Names:
  • Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
Procedure: Radical Prostatectomy
as per standard care
EXPERIMENTAL: Cohort 2
Intratumoral (IT) Poly ICLC 0.5 mg IT once/week (week 1+2) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intratumoral (IT) Poly ICLC 0.5 mg
0.5 mg IT once/week (week 1)
Biological: Intramuscular (IM) Poly ICLC
1 mg IM twice weekly (weeks 3-6)
Other Names:
  • Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
Procedure: Radical Prostatectomy
as per standard care
EXPERIMENTAL: Cohort 3
Intratumoral (IT) Poly ICLC 1.0 mg IT once/week (week 1) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intramuscular (IM) Poly ICLC
1 mg IM twice weekly (weeks 3-6)
Other Names:
  • Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
Procedure: Radical Prostatectomy
as per standard care
Biological: Intratumoral (IT) Poly ICLC 1.0 mg
1.0 mg IT once/week (week 1)
Other Names:
  • Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
EXPERIMENTAL: Cohort 4
Intratumoral (IT) Poly ICLC 1.0 mg IT once/week (week 1+2) Intramuscular (IM) Poly ICLC 1 mg IM twice weekly (weeks 3-6) Followed by Radical Prostatectomy at Week 10
Biological: Intramuscular (IM) Poly ICLC
1 mg IM twice weekly (weeks 3-6)
Other Names:
  • Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose
Procedure: Radical Prostatectomy
as per standard care
Biological: Intratumoral (IT) Poly ICLC 1.0 mg
1.0 mg IT once/week (week 1)
Other Names:
  • Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-Limiting Toxicity level
Time Frame: Week 6
3+3 dose escalation rules to define a safe dose of preoperative intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) prior to radical prostatectomy
Week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse events
Time Frame: Week 6
Safety as determined by the frequency of adverse events as per the Common Terminology for Adverse Events (CTCAE) version 4.0.
Week 6
Time to PSA progression
Time Frame: up to Week 12
The time to prostate-specific antigen (PSA) progression will be defined as the time to PSA > 0.2 ng/mL
up to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ashutosh Kumar Tewari

Collaborators

Oncovir, Inc.

Investigators

  • Study Director: Sujit S Nair, Ph.D., Icahn School of Medicine at Mount Sinai
  • Principal Investigator: Ashutosh K. Tewari, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 16, 2017

Primary Completion (ACTUAL)

May 6, 2022

Study Completion (ACTUAL)

May 6, 2022

Study Registration Dates

First Submitted

August 23, 2017

First Submitted That Met QC Criteria

August 23, 2017

First Posted (ACTUAL)

August 25, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 10, 2022

Last Update Submitted That Met QC Criteria

September 8, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 15-2081

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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