Basal Cell Cancer of the Skin, Breast Cancer, Melanoma, Sarcoma of the Skin, Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma of the Skin
Conditions
Keywords
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
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.
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.
Interventions
DRUGPoly-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.
Sponsors
Oncovir, Inc.
Nina Bhardwaj
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Stage 4 Cancer 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 | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive disease | 7 |
Baseline characteristics
| Characteristic | Participants With Stage 4 Cancer |
|---|---|
| Age, Continuous | 70 years |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Progression-free Survival
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Stage 4 Cancer | Progression-free Survival | 41 weeks |
Secondary
Therapeutic Effect in Treated Patients
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
Population: study terminated early, data not collected. study terminated before all study visits completed. this 24 month visit was not done.
Other Pre-specified
Overall Survival in Treated Patients
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Stage 4 Cancer | Overall Survival in Treated Patients | 8 Participants |