Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC)

• Sponsor: Nina Bhardwaj (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01984892
• Collaborator: Oncovir, Inc. (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to test the safety of a course of injections containing Poly-ICLC in patients with advanced solid tumors that can be easily and safely reached with a needle.

Poly-ICLC is a compound that has been used to help the body in its fight against cancer.

Condition or Disease	Intervention/Treatment	Phase
Melanoma; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma of the Skin; Sarcoma of the Skin; Basal Cell Cancer of the Skin; Breast Cancer	Drug: Poly-ICLC	Phase 2

Detailed Description

We hypothesize that this therapeutic in-situ autovaccination strategy is comprised of three immunomodulatory steps. The first is the innate immune local tumor killing induced by intratumoral Hiltonol (via NK, TNF, etc). A very close second step is optimal Th1-weighted priming through the in-situ combination of the poly-ICLC danger signal with the tumor antigens released in step 1 and further processed and cross-presented by poly-ICLC activated mDC, etc. The repeated administration of the Hiltonol danger signal IT in the context of the patient's own tumor antigens and in a way that mimics a natural viral infection may be critical to this step. Once the system is optimally primed, the third step is targeting and maintenance of the immune response and its facilitation at remote tumor sites with IM poly-ICLC through chemokine release, inflammasome activation and other costimulatory factors.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC): A Phase II Clinical Study
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IT and IM injections Poly-ICLC Enrolled patients will receive two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle.

Drug: Poly-ICLC; Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy Follow Up via phone every 3 months for 30months, after completion of treatments.; Other Names: Hiltonol®

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [average 52 weeks]

   Progression-free survival defined as the time in weeks from study entry until tumor progression defined using the Wolchok criteria or death. Patients who are alive and free from progression on the date of closing follow-up will be censored on that date. In order to minimize the potential for misdiagnosis of pseudoprogression, related to early inflammation, tumor measurement for determination of progression will be made at the earliest at 26 weeks.

Secondary Outcome Measures

1. Therapeutic Effect in Treated Patients [24 months]

   Induction of innate and/or an adaptive, specific anti-tumor T cell immune response in the injected tumor lesion and also systemically.

Other Outcome Measures

1. Overall Survival in Treated Patients [up to 30 months]

   Patients who are alive on the date of closing follow-up, or 30 months after completing all study treatments, will be censored on that date

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of melanoma, squamous head and neck cancer, sarcoma, squamous cell carcinoma of the skin, basal cell skin cancer, or breast cancer

• Sarcoma Patients must be @ least14 yrs of age; all others 18 yrs of age or older.

• Un-resectable disease. Patients with resectable disease may be enrolled after having refused surgery and documented consultation with a surgeon.

• Disease progressed through @ least 1 systemic therapy or through local irradiation within the preceding 6 mos.

• Radiologically or visually measurable recurrent or metastatic disease and @ least 10mm in longest dimension.

• At least 1 accessible primary or metastatic tumor site that can be readily injected IT with poly-ICLC with or without ultrasound guidance. Lesion can be superficial cutaneous, subcutaneous or within a readily accessible lymph node & must measure @ least 10mm in longest dimension.

• Tumor site injection cannot have been irradiated within 8 wks of C1D1

• ECOG performance status ≤ 2.

• Normal hematologic, renal & liver function. INR<2 if off of anticoagulation. Patients on anticoagulation therapy with an INR>2 may be enrolled at the discretion of the investigator.

• Patients able to provide informed consent.

• Must agree to follow acceptable birth control methods and continue for @ least 2 mos. after last poly-ICLC dose. Women of childbearing potential must have a (-) pregnancy test.

Exclusion Criteria:

• Serious concurrent infection or medical illness.

• Bulky intracranial metastatic disease with shift of midline structures or progressive brain metastasis. Administration of immunotherapy or conventional chemotherapy treatments for metastatic cancer within 4 wks of C1D1

• Radiation treatments within 4 wks of C1D1

• AIDS defined as a CD4 count < then 200 in the context of HIV sero-positivity or chronically is taking immunosuppressive medication such as steroids or transplant related medications.

• Life expectancy of < than 6 mos.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029

Sponsors and Collaborators

• Nina Bhardwaj
• Oncovir, Inc.

Investigators

• Principal Investigator: Nina Bhardwaj, MD, PhD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Nina Bhardwaj, Director, Immunotherapy Program, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01984892
• Other Study ID Numbers: GCO 13-1687; BB-43984
• First Posted: Nov 15, 2013
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Nina Bhardwaj, Director, Immunotherapy Program, Icahn School of Medicine at Mount Sinai: Autologous Vaccination; Intratumoral Injections; Intramuscular Injections; Advanced Accessible Solid Tumors; Poly-ICLC; Phase II Clinical Trial; Safety; Efficacy; Autovaccination; In Situ; Host Targeted Strategy; Overall Survival; Immunotherapy; Adjuvant
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Basal Cell; Carcinoma, Basal Cell; Skin Neoplasms; Poly ICLC

Study Results

Participant Flow

Arm/Group Title	IT and IM Injections Poly-ICLC
Arm/Group Description	Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle. Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy
Period Title: Overall Study
STARTED	8
COMPLETED	1
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Participants With Stage 4 Cancer
Arm/Group Description	Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle. Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy
Overall Participants	8
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70
Sex: Female, Male (Count of Participants)
Female	1 12.5%
Male	7 87.5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression-free survival defined as the time in weeks from study entry until tumor progression defined using the Wolchok criteria or death. Patients who are alive and free from progression on the date of closing follow-up will be censored on that date. In order to minimize the potential for misdiagnosis of pseudoprogression, related to early inflammation, tumor measurement for determination of progression will be made at the earliest at 26 weeks.
Time Frame	average 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Stage 4 Cancer
Arm/Group Description	Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle. Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy
Measure Participants	1
Number [weeks]	41

2. Secondary Outcome

Title	Therapeutic Effect in Treated Patients
Description	Induction of innate and/or an adaptive, specific anti-tumor T cell immune response in the injected tumor lesion and also systemically.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

study terminated early, data not collected. study terminated before all study visits completed. this 24 month visit was not done.

Arm/Group Title	Participants With Stage 4 Cancer
Arm/Group Description	Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle. Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy
Measure Participants	0

3. Other Pre-specified Outcome

Title	Overall Survival in Treated Patients
Description	Patients who are alive on the date of closing follow-up, or 30 months after completing all study treatments, will be censored on that date
Time Frame	up to 30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Stage 4 Cancer
Arm/Group Description	Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle. Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy
Measure Participants	8
Count of Participants [Participants]	8 100%

Adverse Events

Arm/Group Title	Participants With Stage 4 Cancer
Arm/Group Description	Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle. Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks. Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms. Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan. Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks. Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation. Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy
All Cause Mortality
	Participants With Stage 4 Cancer
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Participants With Stage 4 Cancer
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Participants With Stage 4 Cancer
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
General disorders
Fatigue	2/8 (25%)
Musculoskeletal and connective tissue disorders
Periosteal inflammation and necrosis	1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.