AzTrials
AzTrials

Prostate CancerPhase 1NCT03262103

Neoadjuvant Hiltonol® (PolyICLC) for Prostate Cancer

A Phase 1 study testing Intratumoral (IT) Poly ICLC 0.5 mg, Intratumoral (IT) Poly ICLC 1.0 mg and Intramuscular (IM) Poly ICLC in people with Prostate Cancer, run by Ashutosh Kumar Tewari at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Intratumoral (IT) Poly ICLC 0.5 mg, Intratumoral (IT) Poly ICLC 1.0 mg and Intramuscular (IM) Poly ICLC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
16 Jun 2017to 6 May 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 33Show fewer
  • 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.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions
Prostate Cancer
Being tested
Intratumoral (IT) Poly ICLC 0.5 mg, Intratumoral (IT) Poly ICLC 1.0 mg, Intramuscular (IM) Poly ICLC, Radical Prostatectomy
Keywords
Prostate Cancer, Gleason 7-10, Immunotherapy, Neoadjuvant
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intratumoral (IT) Poly ICLC 0.5 mgBiological

    0.5 mg IT once/week (week 1)

  • Intratumoral (IT) Poly ICLC 1.0 mgBiological

    Also called Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose

    1.0 mg IT once/week (week 1)

  • Intramuscular (IM) Poly ICLCBiological

    Also called Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose

    1 mg IM twice weekly (weeks 3-6)

  • Radical ProstatectomyProcedure or surgery

    as per standard care

Study groups in NCT03262103
Study groupRoleWhat they receive
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
Receives: Biological: Intratumoral (IT) Poly ICLC 0.5 mg; Biological: Intramuscular (IM) Poly ICLC; Procedure: Radical Prostatectomy
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
Receives: Biological: Intratumoral (IT) Poly ICLC 0.5 mg; Biological: Intramuscular (IM) Poly ICLC; Procedure: Radical Prostatectomy
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
Receives: Biological: Intratumoral (IT) Poly ICLC 1.0 mg; Biological: Intramuscular (IM) Poly ICLC; Procedure: Radical Prostatectomy
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
Receives: Biological: Intratumoral (IT) Poly ICLC 1.0 mg; Biological: Intramuscular (IM) Poly ICLC; Procedure: Radical Prostatectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-Limiting Toxicity level

    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

    Measured: Week 6

Secondary outcomes (2)

  1. Number of adverse events

    Safety as determined by the frequency of adverse events as per the Common Terminology for Adverse Events (CTCAE) version 4.0.

    Measured: Week 6

  2. Time to PSA progression

    The time to prostate-specific antigen (PSA) progression will be defined as the time to PSA > 0.2 ng/mL

    Measured: up to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2017
  2. Study start16 Jun 2017
  3. Primary completion6 May 2022
  4. Study completion6 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03262103
Sponsor's protocol ID
GCO 15-2081
Status last verified
Sep 2022
First submitted
23 Aug 2017
Last updated
10 Sep 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. doi: 10.3322/caac.21208. Epub 2014 Jan 7.

    PubMed 24399786

  • Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999 May 5;281(17):1591-7. doi: 10.1001/jama.281.17.1591.

    PubMed 10235151

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

    PubMed 20818862

  • Sonpavde G, Di Lorenzo G, Higano CS, Kantoff PW, Madan R, Shore ND. The role of sipuleucel-T in therapy for castration-resistant prostate cancer: a critical analysis of the literature. Eur Urol. 2012 Apr;61(4):639-47. doi: 10.1016/j.eururo.2011.10.027. Epub 2011 Oct 24.

    PubMed 22036643

  • Levy HB, Levine AS. Antitumor effects of interferon and poly ICLC, and their possible utility as anti-neoplastic agents in man. Tex Rep Biol Med. 1981-1982;41:653-62. No abstract available.

    PubMed 6189230

  • Caskey M, Lefebvre F, Filali-Mouhim A, Cameron MJ, Goulet JP, Haddad EK, Breton G, Trumpfheller C, Pollak S, Shimeliovich I, Duque-Alarcon A, Pan L, Nelkenbaum A, Salazar AM, Schlesinger SJ, Steinman RM, Sekaly RP. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med. 2011 Nov 21;208(12):2357-66. doi: 10.1084/jem.20111171. Epub 2011 Nov 7.

    PubMed 22065672

  • Zhu X, Fallert-Junecko BA, Fujita M, Ueda R, Kohanbash G, Kastenhuber ER, McDonald HA, Liu Y, Kalinski P, Reinhart TA, Salazar AM, Okada H. Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners. Cancer Immunol Immunother. 2010 Sep;59(9):1401-9. doi: 10.1007/s00262-010-0876-3. Epub 2010 Jun 12.

    PubMed 20549206

  • Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM, Lieberman FS. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with alpha-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011 Jan 20;29(3):330-6. doi: 10.1200/JCO.2010.30.7744. Epub 2010 Dec 13.

    PubMed 21149657

  • Chew V, Tow C, Huang C, Bard-Chapeau E, Copeland NG, Jenkins NA, Weber A, Lim KH, Toh HC, Heikenwalder M, Ng IO, Nardin A, Abastado JP. Toll-like receptor 3 expressing tumor parenchyma and infiltrating natural killer cells in hepatocellular carcinoma patients. J Natl Cancer Inst. 2012 Dec 5;104(23):1796-807. doi: 10.1093/jnci/djs436. Epub 2012 Nov 29.

    PubMed 23197495

  • Sivori S, Falco M, Della Chiesa M, Carlomagno S, Vitale M, Moretta L, Moretta A. CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10116-21. doi: 10.1073/pnas.0403744101. Epub 2004 Jun 24.

    PubMed 15218108

  • North RJ, Dunn PL, Havell EA. A role for tumor necrosis factor in poly(I:C)-induced hemorrhagic necrosis and T-cell-dependent regression of a murine sarcoma. J Interferon Res. 1991 Dec;11(6):333-40. doi: 10.1089/jir.1991.11.333.

    PubMed 1839310

  • Bogunovic D, Manches O, Godefroy E, Yewdall A, Gallois A, Salazar AM, Marie I, Levy DE, Bhardwaj N. TLR4 engagement during TLR3-induced proinflammatory signaling in dendritic cells promotes IL-10-mediated suppression of antitumor immunity. Cancer Res. 2011 Aug 15;71(16):5467-76. doi: 10.1158/0008-5472.CAN-10-3988. Epub 2011 Jul 5.

    PubMed 21730023

  • Black PL, Hartmann D, Pennington R, Phillips H, Schneider M, Tribble HR, Talmadge JE. Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethyl cellulose [Poly(I,C)-LC]. Int J Immunopharmacol. 1992 Nov;14(8):1341-53. doi: 10.1016/0192-0561(92)90005-6.

    PubMed 1464467

  • Kajiwara K, Morishima H, Akiyama K, Yanagihara Y. Expression and function of the inducible costimulator ligand B7-H2 in human airway smooth muscle cells. Allergol Int. 2009 Dec;58(4):573-83. doi: 10.2332/allergolint.09-OA-0113. Epub 2009 Sep 25.

    PubMed 19776675

  • Stevenson HC, Abrams PG, Schoenberger CS, Smalley RB, Herberman RB, Foon KA. A phase I evaluation of poly(I,C)-LC in cancer patients. J Biol Response Mod. 1985 Dec;4(6):650-5.

    PubMed 2418163

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Intratumoral (IT) Poly ICLC 0.5 mg, Intratumoral (IT) Poly ICLC 1.0 mg and Intramuscular (IM) Poly ICLC in people with Prostate Cancer, run by Ashutosh Kumar Tewari at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-Limiting Toxicity level (time frame: Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03262103, which also lists 42 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in