In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC)
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ClinicalTrials.gov Identifier: NCT02423863 |
Recruitment Status :
Completed
First Posted : April 22, 2015
Last Update Posted : December 17, 2020
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Condition or disease | Intervention/treatment | Phase |
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Melanoma Head and Neck Cancer Sarcoma Non-Melanoma Skin Cancers | Biological: Hiltonol | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 26 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC): An Adaptive, Multicenter, Phase II Clinical Study |
Study Start Date : | March 2015 |
Actual Primary Completion Date : | August 31, 2020 |
Actual Study Completion Date : | August 31, 2020 |

Arm | Intervention/treatment |
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Experimental: Hiltonol Poly-ICLC
Open labeled, non randomized adaptive 2-stage design protocol. 21 study subjects were enrolled in stage I of the protocol. Up to an additional 60 patients. . Enrolled study subjects will receive Poly-ICLC (Hiltonol®) treatment alone or in combination with anti-PD-1 (Nivolumab, Pembrolizumab or Cemiplimab) or anti-PD-L1 (Atezolizumab or Durvalumab) over 6 months as defined in study treatment described below. MRI or CT imaging will be done per SOC at screening, 3 and 6-month time points. For purposes of analysis patients enrolled in Stage II of this study will be prospectively identified at initial screening as belonging to statistical Cohorts A, B, or C, which are based on patient status with regard to aPD1/aPDL1 therapy at study entry, (PD, SD, or treatment naïve). For purposes of this study, patient status is considered to be the primary eligibility variable, although sub analyses will also consider histology and particular checkpoint blocker used when possible. |
Biological: Hiltonol
Wk 1 Days 1, 3 and 5: Poly-ICLC (Hiltonol®) 1 mg (0. 5 ml) IntraTumoral (priming treatment course). Weeks 2-25 Poly-ICLC (Hiltonol®) 1 mg (0.5 ml) IM twice a week with a 48-72 hour interval between the two injections, AND either: No additional immunotherapy OR ONLY ONE of the Anti-PD1 or anti-PDL-1 regimens will be administered, per manufacturer's dosing and clinical oncologist's discretion as follows: (Not to be Administered on the same day as Poly-ICLC [Hiltonol®]) Either Nivolumab, OR Pembrolizumab, OR Atezolizumab, OR Cemiplimab, OR Durvalumab Other Names:
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- Evaluate safety of intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) for treatment of patients with accessible solid tumors, with or with [ Time Frame: Evaluation of response wk 26 ]Wk 26 study subject's response will be defined as BOR (CR, PR, SD) or PD.
- Evaluate therapeutic efficacy assessed by Disease Control (CR, PR, or SD) as defined by the RECIST 1.1 Criteria. [ Time Frame: 6 months ]Week 26 tumor assessment will be performed, an optional biopsy may be performed.
- Determine whether the study regimen of Poly-ICLC will induce an innate and/or an adaptive, specific anti-tumor T cell immune response in the injected tumor lesion and systemically. [ Time Frame: 26 weeks ]Serial blood samples collected at certain time points and processed and used to evaluate humoral and cellular immunity induced by IT and IM polyICLC injections
- Determine the response in injected lesions as defined by change in size at 16 weeks and 26 weeks as assessed by bi-dimensional measurement using RECIST 1.1 criteria. [ Time Frame: 16 weeks and 26 weeks ]In the present protocol, we propose to induce both innate and adaptive cellular immune mechanisms with IT injections of poly-ICLC (Nierkens, den Brock et al. 2008)
- Determine the response in non-injected tumor lesions, both visceral and non-visceral as defined by change in size at 16 weeks and 26 weeks as assessed by bi- dimensional measurement. [ Time Frame: 16 weeks and 26 weeks ]Bi-dimensional measurements will be performed on injected and non-injected lesions at the indicated time points in the study calendar.
- Determine progression free survival at 12, 24, and 36 months in treated study subjects. [ Time Frame: 12, 24 and 36 months ]Up to 5 visible deep measureable lesions will be designated as Target Lesions (index lesions)
- Determine overall survival (OS) in treated study subjects. [ Time Frame: Up to 36 months ]Survival and disease control/progression-free survival (PFS) will be estimated using Kaplan-Meir curves.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
1)1) Histologically confirmed diagnosis of one of the following:
- Melanoma
- Squamous head and neck cancer
- Sarcoma
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Non-Melanoma skin cancers 2) Sarcoma Patients must be 14 years of age or older. All other patients must be 18 years of age or older.
3) Unresectable disease. Patients with resectable disease may be enrolled after having refused surgery after a documented consultation with a surgeon.
4) Radiographic or visually measurable disease based on Response Evaluation Criteria In Solid Tumors, Version 1.1 criteria.
5) At least one accessible primary or metastatic tumor site that can be readily injected IT with poly-ICLC with or without ultrasound guidance. This lesion can be superficial cutaneous, subcutaneous, or within a readily accessible location, including a lymph node, and must measure ≥ 15mm short axis for target.
6) Patients who have received at least 8 weeks of aPD1 or aPDL1 immunotherapy and who have either progressive disease, stable disease or partial response based on RECIST 1.1 criteria are elegible for participation as separate cohorts B or C, with continuation of the aPD1 or aPDL1 therapy at their physician's discretion.
7) ECOG performance status of ≤ 2. 8) Acceptable hematologic, renal and liver function as follows: A) Absolute neutrophil count > 1000/mm3 B) Platelets > 50,000/mm3, C) Creatinine ≤ 2.5 mg/dl, D) Total bilirubin ≤ 1.5 mg/dl, E) Transaminases ≤ 2 times above the upper limits of the institutional normal. F) INR<2 if off of anticoagulation. Patients on anticoagulation therapy with an INR>2 may be enrolled at the discretion of the investigator if they have not had any episodes of severe hemorrhage and if the site to be injected is not located in the oropharynx or another area where achieving homeostasis would be complicated by local anatomy.
9) Patients must be able to provide informed consent. 10) Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Contraception must be continued for at least 2 months following the last dose of poly-ICLC. Women of childbearing potential must have a negative pregnancy test. While animal reproductive studies have been negative, the simulated viral infection and anti-proliferative activity of this experimental drug may theoretically affect the developing fetus or nursing infant.
Cohort Specific Inclusion Criteria (see § 11.6 Evaluation of Best Overall Response (BOR)
Cohort A) 11) Patients who are not receiving an anti-PD-1 or anti-PD-L1 agent,
Cohort B 12) Patients who have received at least 8 weeks of aPD1 or aPDL1 immunotherapy. 13) Patients have progressive disease based on RECIST 1.1 criteria.
Cohort C) 14) Patients who have received at least 8 weeks of aPD1 or aPDL1 immunotherapy. 15) Patients have stable disease or a partial response based on RECIST 1.1 criteria.
4.2 Exclusion Criteria
Patients with any of the following are ineligible for this research study:
- Serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
- Bulky intracranial metastatic disease with shift of midline structures or progressive brain metastasis such that ongoing therapy for these brain metastasis is required at the time of enrollment.
- In the opinion of the local PI: Head and neck cancer patients with airway tumor recurrence that may compromise breathing or swallowing if inflammation or edema is transiently aggravated by Hiltonol® injection. Head and neck cancer patients with tumor invading major blood vessels for whom there may be a risk of blockage or bleeding if inflammation or edema is transiently increased by Hiltonol® injections.
- AIDS defined as a CD4 count less than 200 in the context of HIV sero-positivity or chronically is taking immunosuppressive medication such as steroids or transplant related medications.
- Life expectancy of less than 6 months in the judgment of the study physician.
- Persistent toxicity from recent therapy that has not sufficiently resolved in the judgment of the study physician.
- History of active cancer vaccine immunotherapy in the previous month. Patients who have received at least 8 weeks of aPD1 or aPDL1 immunotherapy and who have either progressive disease, stable disease or partial response based on RECIST 1.1 criteria are elegible for participation and continuation of the aPD1 or aPDL1 therapy at their physician's discretion.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423863
United States, Maryland | |
Chevy Chase RCCA | |
Chevy Chase, Maryland, United States, 20815 | |
Dermatologic Surgery Center Washington DC | |
Chevy Chase, Maryland, United States, 20815 | |
Bay Hematology Oncology | |
Easton, Maryland, United States, 2160l | |
United States, Missouri | |
University of Missouri School of Medicine | |
Columbia, Missouri, United States, 65211-0001 | |
United States, New York | |
Icahn School of Medicine at Mount Sinai | |
New York, New York, United States, 10029 |
Principal Investigator: | Nina Bhardwaj, MD, PhD | Icahn School of Medicine at Mount Sinai | |
Principal Investigator: | David H Smith, MD | Bay Hematology Oncology | |
Principal Investigator: | Kevin Staveley-O'Carroll, MD | University Missouri | |
Principal Investigator: | Frederick P Smith, MD | Chevy Chase, RCCA |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Oncovir, Inc. |
ClinicalTrials.gov Identifier: | NCT02423863 |
Other Study ID Numbers: |
ONC2014-001 1R44CA183075-01A1 ( U.S. NIH Grant/Contract ) |
First Posted: | April 22, 2015 Key Record Dates |
Last Update Posted: | December 17, 2020 |
Last Verified: | September 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Plan Description: | No plan to share data |
Cancer Immunotherapy Intratumoral Injection Multicenter Study |
Autovaccination Solid Tumors anti-PD1 anti-PDL1 |
Head and Neck Neoplasms Skin Neoplasms Neoplasms Neoplasms by Site Skin Diseases Pembrolizumab Nivolumab Durvalumab Cemiplimab |
Atezolizumab Poly ICLC Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Interferon Inducers Immunologic Factors Physiological Effects of Drugs |