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In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC)

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ClinicalTrials.gov Identifier: NCT02423863
Recruitment Status : Recruiting
First Posted : April 22, 2015
Last Update Posted : September 10, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Icahn School of Medicine at Mount Sinai
Bay Hematology Oncology
University of Pittsburgh
National Cancer Institute (NCI)
University of Missouri-Columbia
Medical University of South Carolina
Chevy Chase Regional Cancer Care Associates LLC
Dermatologic Surgery Center of Washington LLC and Skin Cancer Treatment Center
Information provided by (Responsible Party):
Oncovir, Inc.

Study Description
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Brief Summary:
The purpose of this study is to evaluate the safety of sequential intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) for treatment of study subjects with advanced accessible solid tumors

Condition or disease Intervention/treatment Phase
Melanoma Head and Neck Cancer Sarcoma Non-Melanoma Skin Cancers Biological: Hiltonol Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Hiltonol Poly-ICLC
This is an adaptive 2 stage design protocol. A total of up to 90 study subjects will be enrolled. Up to 30 total study subjects with one of the four indications above will be treated in stage I of the protocol. At the end of stage I, a planned interim analysis will be conducted and one of the four indications will be selected for enrollment of up to an additional 60 patients, for a total of 90 patients the study. At the conclusion of Stage I, the protocol will be amended based on the planned interim data analysis.
 Biological: Hiltonol
Priming treatment course, which consists of a total of 6 IT injections (Cycle 1 Week 1 and Cycle 2 Week 14) of 0.5 mg poly-ICLC followed by boosting treatment course, consisting of 1 mg IM injections of Poly-ICLC twice weekly for weeks 2-13 and weeks 15-25. Study subject's response will be defined as Disease Control (CR, PR, SD) or PD
Other Name: Poly-ICLC


Outcome Measures
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Primary Outcome Measures :
  1. Evaluate the safety of sequential intratumoral (IT) plus intramuscular (IM) Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC, Hiltonol®) for treatment of study subjects with advanced accessible solid tumors [ Time Frame: Evaluation of response wk 26 ]
    Study subjects will be assessed and response determined using the irRC criteria. This will include measurement of accessible lesions as well as CT scan of the chest, abdomen and pelvis and extremities or neck to assess for response, using Immune related Response Criteria (irRC). MRI of the brain may also be obtained as part of clinical follow of their disease, if clinically indicated as per standard clinical protocol. Study subject's response will be defined as Disease Control (CR, PR, SD) or PD. If tumors are present and accessible, biopsies of the injected tumor as well as of a non-targeted/non-injected tumor will also be obtained at week 26.

  2. To evaluate therapeutic efficacy in treated study subjects as assessed by Disease Control (CR,PR, or SD) as defined by the Immune-related Response Criteria (irRC) and recorded at the 6 month timepoint only, compared to baseline. [ Time Frame: 6 months ]
    Study subjects with CR, PR, or SD may be offered maintenance therapy from week 27 to 36, with administration of 1 mg IM Poly-ICLC twice weekly as per below schema. At week 36 a repeat tumor assessment, including optional tumor biopsy, will be performed.


Secondary Outcome Measures :
  1. 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 baseline, and at selected time points during and post treatment as detailed in the study calendar will be processed to collect plasma/serum and peripheral blood mononuclear cells (PBMCs) which be used to evaluate humoral and cellular immunity induced by IT and IM polyICLC injections

  2. 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 IrRC 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)

  3. 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.

  4. Determine progression free survival at 12, 24, and 36 months in treated study subjects. [ Time Frame: 12, 24 and 36 months ]
    Up to 10 lesions, including the target lesion, will be measured. If the target lesion is measured under ultrasound guidance, it will be measured under ultrasound guidance. Skin lesions will be measured using a ruler or calipers. Skin lesions which are completely flat, do not protrude above the skin surface and are stable in size from the prior visit will be considered scars and scored as a 0.

  5. Determine overall survival (OS) in treated study subjects. [ Time Frame: Up to 36 months ]
    Overall survival will be estimated using a Kaplan-Meier curve to describe survival from enrollment to death from any cause or until censoring.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed diagnosis of one of the following:

    • Melanoma
    • Squamous head and neck cancer
    • Sarcoma
    • 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. Radiologically or visually measurable recurrent or metastatic disease that is measurable and at least 10mm in longest dimension.
  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 lymph node and must measure at least 10 mm in longest dimension.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

  7. Acceptable hematologic, renal and liver function as follows:

    • Absolute neutrophil count > 1000/mm3,
    • Platelets > 50,000/mm3,
    • Creatinine ≤ 2.5 mg/dl,
    • Total bilirubin ≤ 1.5mg/dl,
    • Transaminases ≤ 2 times above the upper limits of the institutional normal, - INR<2 (international normalized ratio) 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.
  8. Patients must be able to provide informed consent.
  9. 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.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. AIDS defined as a CD4 (cluster of differentiation 4) count less then 200 in the context of HIV sero-positivity or chronically is taking immunosuppressive medication such as steroids or transplant related medications.
  5. Life expectancy of less than 6 months in the judgment of the study physician.
  6. Persistent toxicity from recent therapy that has not sufficiently resolved in the judgment of the study physician.
  7. History of active immunotherapy in the previous month.
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
Contact: Andres M Salazar, MD 202 342 1726 asalazar@oncovir.com
Contact: Rose Marie Holman, MA 917 885 9680 rmholman@oncovir.com

Locations
United States, Maryland
Chevy Chase RCCA Recruiting
Chevy Chase, Maryland, United States, 20815
Contact: Frederick P Smith, MD    301-657-8587    fpsonc@aol.com   
Contact: Susan Bendel, RN    301- 657- 8587    sbendel@regionalcancercare.org   
Dermatologic Surgery Center Washington DC Recruiting
Chevy Chase, Maryland, United States, 20815
Contact: Maral K Skelsey, MD    301-652-8081    dr.maral.skelsey@mohs-md.com   
Contact: Xiaophin Bai, MD    301 652 8081    officemanager@mohs-md.com   
Bay Hematology Oncology Recruiting
Easton, Maryland, United States, 2160l
Contact: David Smith, MD    410-820-5945    md@bayonc.com   
Contact: Amy Wright, RN    410 820 5945 ext 4    amy@bayonc.com   
United States, Missouri
University of Missouri School of Medicine Recruiting
Columbia, Missouri, United States, 65211-0001
Contact: Kevin Staveley-O'Carroll, MD    843-696-8164    staveleyocarrollk@health.missouri.edu   
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Nina Bhardwaj, MD, PhD    212-824-8427    nina.bhardwaj@mssm.edu   
Contact: Erlinda Sacris, RN,OCN    212 824 9359    erlinda.sacris@mssm.edu   
Principal Investigator: Nina Bhardwaj, MD, PhD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Melissa Burgess,, MD    412-623-3205    burgessma@upmc.edu   
United States, South Carolina
Medical University of South Carolina Not yet recruiting
Charleston, South Carolina, United States, 29425-8150
Contact: John Wrangle, MD, MPH    843-792-7786    wrangle@musc.edu   
Sponsors and Collaborators
Oncovir, Inc.
National Institutes of Health (NIH)
Icahn School of Medicine at Mount Sinai
Bay Hematology Oncology
University of Pittsburgh
National Cancer Institute (NCI)
University of Missouri-Columbia
Medical University of South Carolina
Chevy Chase Regional Cancer Care Associates LLC
Dermatologic Surgery Center of Washington LLC and Skin Cancer Treatment Center
Investigators
Principal Investigator: Nina Bhardwaj, MD, PhD Icahn School of Medicine at Mount Sinai
Principal Investigator: Erlich Rodrigro, MD Bay Hematology Oncology
Principal Investigator: Dong M Shin, MD, FACP Emory University School of Medicine, Winship Cancer Institute
Principal Investigator: Melissa Burgess, MD University of Pittsburgh
Principal Investigator: Kevin Staveley-O'Carroll, MD University Missouri
Principal Investigator: John Wrangle, MD, PhD Medical University of South Carolina
Principal Investigator: Frederick P Smith, MD Chevy Chase, RCCA
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Oncovir, Inc.
ClinicalTrials.gov Identifier: NCT02423863     History of Changes
Other Study ID Numbers: ONC2014-001
1R44CA183075-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 22, 2015    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share data

Keywords provided by Oncovir, Inc.:
Cancer
Immunotherapy
Intratumoral Injection
 Multicenter Study
Autovaccination
Solid Tumors

Additional relevant MeSH terms:
Head and Neck Neoplasms
Skin Neoplasms
Neoplasms by Site
Neoplasms
Skin Diseases
Poly ICLC
Poly I-C
Carboxymethylcellulose Sodium
 Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents