Clinical Trials /

Neoadjuvant Hiltonol® (PolyICLC) for Prostate Cancer

NCT03262103

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Hiltonol® (PolyICLC) for Prostate Cancer
  • Official Title: Phase I Study of In Situ Autologous Vaccination Against Prostate Cancer With Intratumoral and Systemic Hiltonol® (Poly-ICLC) Prior To Radical Prostatectomy

Clinical Trial IDs

  • ORG STUDY ID: GCO 15-2081
  • NCT ID: NCT03262103

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Intratumoral (IT) Poly ICLC 0.5 mgCohort 1
Intratumoral (IT) Poly ICLC 1.0 mgPolyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcelluloseCohort 3
Intramuscular (IM) Poly ICLCPolyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcelluloseCohort 1

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalIntratumoral (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
  • Intratumoral (IT) Poly ICLC 0.5 mg
  • Intramuscular (IM) Poly ICLC
Cohort 2ExperimentalIntratumoral (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
  • Intratumoral (IT) Poly ICLC 0.5 mg
  • Intramuscular (IM) Poly ICLC
Cohort 3ExperimentalIntratumoral (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
  • Intratumoral (IT) Poly ICLC 1.0 mg
  • Intramuscular (IM) Poly ICLC
Cohort 4ExperimentalIntratumoral (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
  • Intratumoral (IT) Poly ICLC 1.0 mg
  • Intramuscular (IM) Poly ICLC

Eligibility Criteria

        Inclusion Criteria:

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

          2. Age > 18 years at the time of consent.

          3. ECOG Performance Status of 0-1 within 14 days prior to being registered for protocol
             therapy (Study Procedure Manual).

          4. Histologically confirmed adenocarcinoma of the prostate (with previous diagnostic
             tissue available for tumor marker analysis).

          5. Gleason 7 - 10, cT2a - cT3b adenocarcinoma of the prostate with plans for radical
             prostatectomy

          6. PSA ≥ 4 ng/ml

          7. Tumor visible on multiparametric MRI

          8. Tolerated previous transrectal ultrasound guided biopsy procedure under local
             anesthetic

             a. Uncomplicated previous TRUS biopsy procedure (i.e., no prior hospitalization due to
             sepsis, prostatic abscess or severe hemorrhage following TRUS prostate biopsy)

          9. Willing to undergo the intra-tumoral (IT) injection of the Poly-ICLC into the
             prostatic tumor as per the protocol

         10. 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.

         11. No prior radiation therapy (external beam or brachytherapy) to the pelvis or prostate.

         12. No clinically significant infections as judged by the treating investigator.

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

               1. Recurrent urinary tract infections or history of prostatitis within 3 months
                  prior to enrollment into the study.

               2. Urine analysis positive for nitrites and leucocyte esterase. Such patients could
                  be considered for the study after treatment and resolution of the infection.

               3. Active proctitis

               4. History of prostatic abscess

               5. Taking immunosuppressive medication including systemic corticosteroids

               6. Active hematologic malignancy

         14. No uncontrolled angina, congestive heart failure or MI within 6 months.

         15. No known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies), active
             Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is
             detected).

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

         17. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Limiting Toxicity level
Time Frame:Week 6
Safety Issue:
Description: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

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ashutosh Kumar Tewari

Trial Keywords

  • Prostate Cancer
  • Gleason 8-10
  • Immunotherapy
  • Neoadjuvant

Last Updated

November 1, 2018