MelanomaPhase 2Poly-ICLCNCT02423863
In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol®
A Phase 2 study testing Hiltonol in people with Melanoma and Head and Neck Cancer, run by Oncovir, Inc. at 5 sites in United States.
Trial 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 accessible solid tumors, with or without checkpoint blockers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Head and Neck Cancer, Sarcoma
- What is being tested?
- Hiltonol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2015to 31 Aug 2020
- Phase
- Phase 2
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1)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.
Show all 24Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Chevy Chase RCCA
Chevy Chase, Maryland, 20815
Dermatologic Surgery Center Washington DC
Chevy Chase, Maryland, 20815
University of Missouri School of Medicine
Columbia, Missouri, 65211-0001
Bay Hematology Oncology
Easton, Maryland, 2160l
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC): An Adaptive, Multicenter, Phase II Clinical Study
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 accessible solid tumors, with or without checkpoint blockers. 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.
Read the detailed description
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) per section 11.5. 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. Please see section 12 (Statistical Analysis) for further discussion.
Week 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 following 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 (Opdivo), OR
- Pembrolizumab (Keytruda), OR
- Atezolizumab (Tecentriq) OR
- Cemiplimab (Libtayo) OR
- Durvalumab (Imfinzi)
NOTE: It is recognized that some patients will have already been on anti-PD-1 or anti-PD-L1 at the time of study entry. Such patients will not have their checkpoint blocker therapy interrupted, but will be started on Poly-ICLC on week one, as above
If well tolerated they continue at full dose of 1 mg IM twice weekly through week 25. Anti-PD-1 or anti-PD-L1 per manufacturers package insert begins on week two and continues through week 25 or beyond per standard of care at physician's discretion. After the end of Poly-ICLC treatment at week 25, aPD1 or aPDL1 can be continued at the discretion of the patient and treating physician, per SOC, independent of this protocol.
At week 26 study subjects will be assessed and response determined using the RECIST 1.1 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 RECIST 1.1. 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 BOR (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.
Study subjects with CR, PR, or SD may be offered an additional treatment cycle depending on study subject's health status, costs and/or drug availability. At week 26 a repeat tumor assessment will be performed, an optional biopsy may be performed.
Follow up Period:
After completion of study treatment, study subjects may be contacted by telephone at least twice over 12 months, or longer with patient consent to inquire on their health status (e.g., alive, remission, progressive disease, on new cancer treatment). Study subjects with an initial tumor response but then long-term recurrence during the follow up period may be offered additional cycles of treatment depending on the study subject's health status, costs and/or drug availability.
- Conditions
- Melanoma, Head and Neck Cancer, Sarcoma, Non-Melanoma Skin Cancers
- Being tested
- Hiltonol
- Keywords
- Cancer, Immunotherapy, Intratumoral Injection, Multicenter Study, Autovaccination, Solid Tumors, anti-PD1, anti-PDL1
- Medical subject headings
- Melanoma, Head and Neck Neoplasms, Sarcoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HiltonolBiological
Also called Poly-ICLC, Nivolumab, Pembrolizumab, Atezolizumab
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
| Study group | Role | What they receive |
|---|---|---|
| Hiltonol Poly-ICLC | Experimental | 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. Receives: Biological: Hiltonol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Wk 26 study subject's response will be defined as BOR (CR, PR, SD) or PD.
Measured: Evaluation of response wk 26
Evaluate therapeutic efficacy assessed by Disease Control (CR, PR, or SD) as defined by the RECIST 1.1 Criteria.
Week 26 tumor assessment will be performed, an optional biopsy may be performed.
Measured: 6 months
Secondary outcomes (5)
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.
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
Measured: 26 weeks
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.
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)
Measured: 16 weeks and 26 weeks
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.
Bi-dimensional measurements will be performed on injected and non-injected lesions at the indicated time points in the study calendar.
Measured: 16 weeks and 26 weeks
Determine progression free survival at 12, 24, and 36 months in treated study subjects.
Up to 5 visible deep measureable lesions will be designated as Target Lesions (index lesions)
Measured: 12, 24 and 36 months
Determine overall survival (OS) in treated study subjects.
Survival and disease control/progression-free survival (PFS) will be estimated using Kaplan-Meir curves.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study startMar 2015
- Primary completion31 Aug 2020
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncovir, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), Icahn School of Medicine at Mount Sinai, Bay Hematology Oncology, National Cancer Institute (NCI), University of Missouri-Columbia, Chevy Chase Regional Cancer Care Associates LLC, Dermatologic Surgery Center of Washington LLC and Skin Cancer Treatment Center
- Responsible party
- Sponsor
- Investigators
- Nina Bhardwaj, MD, PhD, Principal investigator, Icahn School of Medicine at Mount SinaiDavid H Smith, MD, Principal investigator, Bay Hematology OncologyKevin Staveley-O'Carroll, MD, Principal investigator, University MissouriFrederick P Smith, MD, Principal investigator, Chevy Chase, RCCA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423863
- Sponsor's protocol ID
- ONC2014-001
- Other IDs
- 1R44CA183075-01A1
- Acronym
- Poly-ICLC
- Status last verified
- Sep 2017
- First submitted
- 13 Apr 2015
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: No plan to share data
Publications
Bosio CM, Aman MJ, Grogan C, Hogan R, Ruthel G, Negley D, Mohamadzadeh M, Bavari S, Schmaljohn A. Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation. J Infect Dis. 2003 Dec 1;188(11):1630-8. doi: 10.1086/379199. Epub 2003 Nov 14.
PubMed 14639532Cella M, Salio M, Sakakibara Y, Langen H, Julkunen I, Lanzavecchia A. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J Exp Med. 1999 Mar 1;189(5):821-9. doi: 10.1084/jem.189.5.821.
PubMed 10049946Cho HI, Celis E. Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. Cancer Res. 2009 Dec 1;69(23):9012-9. doi: 10.1158/0008-5472.CAN-09-2019. Epub 2009 Nov 10.
PubMed 19903852Davies ME, Field AK. Effect of poly I:C/poly-L-lysine (poly ICL) on the development of murine osteogenic sarcoma. J Interferon Res. 1983;3(1):89-95. doi: 10.1089/jir.1983.3.89.
PubMed 6573430Geiss G, Jin G, Guo J, Bumgarner R, Katze MG, Sen GC. A comprehensive view of regulation of gene expression by double-stranded RNA-mediated cell signaling. J Biol Chem. 2001 Aug 10;276(32):30178-82. doi: 10.1074/jbc.c100137200.
PubMed 11487589Houot R, Levy R. T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy. Blood. 2009 Apr 9;113(15):3546-52. doi: 10.1182/blood-2008-07-170274. Epub 2008 Oct 21.
PubMed 18941113Huang CC, Duffy KE, San Mateo LR, Amegadzie BY, Sarisky RT, Mbow ML. A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells. Physiol Genomics. 2006 Jul 12;26(2):125-33. doi: 10.1152/physiolgenomics.00002.2006. Epub 2006 Mar 22.
PubMed 16554548Kajiwara 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 19776675Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med. 2009 Jul 6;206(7):1589-602. doi: 10.1084/jem.20090247. Epub 2009 Jun 29.
PubMed 19564349Marcus PI, Sekellick MJ. Combined sequential treatment with interferon and dsRNA abrogates virus resistance to interferon action. J Interferon Cytokine Res. 2001 Jun;21(6):423-9. doi: 10.1089/107999001750277907.
PubMed 11440640Morgan ET, Norman CA. Pretranslational suppression of cytochrome P-450h (IIC11) gene expression in rat liver after administration of interferon inducers. Drug Metab Dispos. 1990 Sep-Oct;18(5):649-53.
PubMed 1706245Nierkens S, den Brok MH, Sutmuller RP, Grauer OM, Bennink E, Morgan ME, Figdor CG, Ruers TJ, Adema GJ. In vivo colocalization of antigen and CpG [corrected] within dendritic cells is associated with the efficacy of cancer immunotherapy. Cancer Res. 2008 Jul 1;68(13):5390-6. doi: 10.1158/0008-5472.CAN-07-6023.
PubMed 18593941North 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 1839310Pilaro AM, Taub DD, McCormick KL, Williams HM, Sayers TJ, Fogler WE, Wiltrout RH. TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma. J Immunol. 1994 Jul 1;153(1):333-42.
PubMed 8207246Salazar AM, Levy HB, Ondra S, Kende M, Scherokman B, Brown D, Mena H, Martin N, Schwab K, Donovan D, Dougherty D, Pulliam M, Ippolito M, Graves M, Brown H, Ommaya A. Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study. Neurosurgery. 1996 Jun;38(6):1096-103; discussion 1103-4.
PubMed 8727138
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Situ, Autologous Therapeutic Vaccination Against Solid Cancers With Intratumoral Hiltonol® (Poly-ICLC): An Adaptive, Multicenter, Phase II Clinical Study
- ClinicalTrials.gov ID
- NCT02423863
- Acronym / sponsor ID
- Poly-ICLC / ONC2014-001
- Conditions
- Melanoma, Head and Neck Cancer, Sarcoma, Non-Melanoma Skin Cancers
- Keywords
- Cancer, Immunotherapy, Intratumoral Injection, Multicenter Study, Autovaccination, Solid Tumors, anti-PD1, anti-PDL1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Oncovir, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), Icahn School of Medicine at Mount Sinai, Bay Hematology Oncology, National Cancer Institute (NCI), University of Missouri-Columbia, Chevy Chase Regional Cancer Care Associates LLC, Dermatologic Surgery Center of Washington LLC and Skin Cancer Treatment Center
- Study start
- Mar 2015
- Primary completion
- 31 Aug 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 accessible solid tumors, with or without checkpoint blockers. 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.
Detailed description
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) per section 11.5. 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. Please see section 12 (Statistical Analysis) for further discussion.
Week 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 following 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 (Opdivo), OR
- Pembrolizumab (Keytruda), OR
- Atezolizumab (Tecentriq) OR
- Cemiplimab (Libtayo) OR
- Durvalumab (Imfinzi)
NOTE: It is recognized that some patients will have already been on anti-PD-1 or anti-PD-L1 at the time of study entry. Such patients will not have their checkpoint blocker therapy interrupted, but will be started on Poly-ICLC on week one, as above
If well tolerated they continue at full dose of 1 mg IM twice weekly through week 25. Anti-PD-1 or anti-PD-L1 per manufacturers package insert begins on week two and continues through week 25 or beyond per standard of care at physician's discretion. After the end of Poly-ICLC treatment at week 25, aPD1 or aPDL1 can be continued at the discretion of the patient and treating physician, per SOC, independent of this protocol.
At week 26 study subjects will be assessed and response determined using the RECIST 1.1 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 RECIST 1.1. 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 BOR (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.
Study subjects with CR, PR, or SD may be offered an additional treatment cycle depending on study subject's health status, costs and/or drug availability. At week 26 a repeat tumor assessment will be performed, an optional biopsy may be performed.
Follow up Period:
After completion of study treatment, study subjects may be contacted by telephone at least twice over 12 months, or longer with patient consent to inquire on their health status (e.g., alive, remission, progressive disease, on new cancer treatment). Study subjects with an initial tumor response but then long-term recurrence during the follow up period may be offered additional cycles of treatment depending on the study subject's health status, costs and/or drug availability.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hiltonol Poly-ICLC | Experimental | Biological: HiltonolOpen 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HiltonolAlso: Poly-ICLC, Nivolumab, Pembrolizumab, AtezolizumabWk 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 | Biological | Hiltonol Poly-ICLC |
Primary outcome
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.
5 secondary outcomes
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
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
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
Determine progression free survival at 12, 24, and 36 months in treated study subjects.
Time frame: 12, 24 and 36 months
Determine overall survival (OS) in treated study subjects.
Time frame: Up to 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Background: PubMed 14639532Bosio CM, Aman MJ, Grogan C, Hogan R, Ruthel G, Negley D, Mohamadzadeh M, Bavari S, Schmaljohn A. Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation. J Infect Dis. 2003 Dec 1;188(11):1630-8. doi: 10.1086/379199. Epub 2003 Nov 14.
- Background: PubMed 10049946Cella M, Salio M, Sakakibara Y, Langen H, Julkunen I, Lanzavecchia A. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J Exp Med. 1999 Mar 1;189(5):821-9. doi: 10.1084/jem.189.5.821.
- Background: PubMed 19903852Cho HI, Celis E. Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. Cancer Res. 2009 Dec 1;69(23):9012-9. doi: 10.1158/0008-5472.CAN-09-2019. Epub 2009 Nov 10.
- Background: PubMed 6573430Davies ME, Field AK. Effect of poly I:C/poly-L-lysine (poly ICL) on the development of murine osteogenic sarcoma. J Interferon Res. 1983;3(1):89-95. doi: 10.1089/jir.1983.3.89.
- Background: PubMed 11487589Geiss G, Jin G, Guo J, Bumgarner R, Katze MG, Sen GC. A comprehensive view of regulation of gene expression by double-stranded RNA-mediated cell signaling. J Biol Chem. 2001 Aug 10;276(32):30178-82. doi: 10.1074/jbc.c100137200.
- Background: PubMed 18941113Houot R, Levy R. T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy. Blood. 2009 Apr 9;113(15):3546-52. doi: 10.1182/blood-2008-07-170274. Epub 2008 Oct 21.
- Background: PubMed 16554548Huang CC, Duffy KE, San Mateo LR, Amegadzie BY, Sarisky RT, Mbow ML. A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells. Physiol Genomics. 2006 Jul 12;26(2):125-33. doi: 10.1152/physiolgenomics.00002.2006. Epub 2006 Mar 22.
- Background: PubMed 19776675Kajiwara 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.
- Background: PubMed 19564349Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med. 2009 Jul 6;206(7):1589-602. doi: 10.1084/jem.20090247. Epub 2009 Jun 29.
- Background: PubMed 11440640Marcus PI, Sekellick MJ. Combined sequential treatment with interferon and dsRNA abrogates virus resistance to interferon action. J Interferon Cytokine Res. 2001 Jun;21(6):423-9. doi: 10.1089/107999001750277907.
- Background: PubMed 1706245Morgan ET, Norman CA. Pretranslational suppression of cytochrome P-450h (IIC11) gene expression in rat liver after administration of interferon inducers. Drug Metab Dispos. 1990 Sep-Oct;18(5):649-53.
- Background: PubMed 18593941Nierkens S, den Brok MH, Sutmuller RP, Grauer OM, Bennink E, Morgan ME, Figdor CG, Ruers TJ, Adema GJ. In vivo colocalization of antigen and CpG [corrected] within dendritic cells is associated with the efficacy of cancer immunotherapy. Cancer Res. 2008 Jul 1;68(13):5390-6. doi: 10.1158/0008-5472.CAN-07-6023.
- Individual participant dataSharing planned: No. No plan to share data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nina Bhardwaj, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
David H Smith, MD principal investigator
Bay Hematology Oncology
Kevin Staveley-O'Carroll, MD principal investigator
University Missouri
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hiltonol in people with Melanoma and Head and Neck Cancer, run by Oncovir, Inc. at 5 sites 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 24 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 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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). The study lists 2 primary outcomes in all. 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 NCT02423863, which also lists 22 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 17 Dec 2020.