Safety and Feasibility of TA-CIN Vaccine in HPV16 Associated Cervical Cancer

Study Overview
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Brief Summary
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This study will be looking at what dose of the TA-CIN vaccine is safe and effective in patients with a history of HPV16-associated cervical cancer.

Detailed Description
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This is a randomized, multi-center, open label pilot study. The primary goal of this study is to determine the safety of TA-CIN vaccine as adjuvant therapy, and to assess evidence of induction of HPV antigen-specific immunologic response when administered at different locations (arm or thigh). In this pilot study, a single dose level (100µg) assessment of the safety and tolerability of administering TA-CIN vaccine three times to either the arm versus the thigh of patients who have previously been treated for HPV16-related cervical cancer in the past year and are documented to have no evidence of disease recurrence based on standard-of-care imaging and/or clinical assessment upon eligibility. A total of 14 patients will be enrolled to assess the safety of TA-CIN vaccine via different injection sites as adjuvant therapy. Safety assessments will continue for a period for 1 month after the last vaccination. Few or no serious adverse events (SAEs) are expected from this regimen and routes of administration. The motivation for the design is to confirm that the dose and site of injection implemented here has minimal or no systemic toxicity, as well as determining the preferred injection site that can elicit more potent immune response. The study will consist of the following parts: Screening evaluation Dosing period and response assessments Follow-up visits after last dose Screening Evaluation: The screening visit will be performed within 60 days of the first study drug administration visit. The study team will check the results of these screening tests to see if patient qualifies to participate. Dosing Period: Those who meet the study requirements during the screening period will then begin the dosing phase of this study. TA-CIN will be given as a single intramuscular injection every 4 weeks for a maximum of 3 times. The location of the injection (arm or thigh) will depend on randomization. Patients will be assessed for safety and response to treatment during this period. Follow-Up Period: Four follow-up evaluations will be performed during a clinic visit after the last dose of the vaccine. These will take place at the following time points: (1) 1-3 weeks after the last dose of the study drug, (2) about 6 months after the last dose of the study drug, (3) about 12 months after the last dose of the study drug, and (4) about 24 months after the last dose of the study drug.

Official Title
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A Pilot Clinical Trial Assessing the Safety and Feasibility of Intramuscular Administration of the TA-CIN Vaccine as Adjuvant Therapy for Patients With History of HPV16 Associated Cervical Cancer

Conditions
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HPV16 Associated Cervical Cancer

Intervention / Treatment
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* Biological: TA-CIN (arm)
* Biological: TA-CIN (thigh)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with HPV16 related stage IB1-IV cervical cancer who completed definitive treatment within 12 months Patients with no evidence of disease recurrence within 8 weeks of enrollment Documented to have HPV16 nucleic acid within the cervical tumor specimen as determined by in situ hybridization Fresh-frozen or paraffin-embedded material must be available for in situ hybridization testing for HPV16 nucleic acid for central confirmation Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ function as defined by study-specified laboratory tests Ability to understand and willingness to sign a written informed consent document Willing and able to comply with study schedule and other protocol requirements Exclusion Criteria: Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive agents such as systemic steroids Prior HPV vaccination Had surgery, chemotherapy, or radiation therapy within 28 days prior to receiving study drug Another investigational product within 28 days prior to receiving study drug Active or chronic HIV, HBV, or HCV infection Pregnant or lactating Patients who have an active autoimmune disease Patients with a recognized immunodeficiency disease or are being chronically treated with immunosuppressive drugs Women of childbearing potential Patients with non-healed wounds A history of current or recent concurrent malignancy (≤5 years) except basal cell cancer. Inability to understand or unwillingness to sign an informed consent document

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TA-CIN administration via thigh<br>Each dose of TA-CIN vaccine is fixed, 100µg. Patients will receive 3 doses of the TA-CIN 4 weeks apart (Weeks 1, 5, and 9), administered in the thigh. Patients will be followed for 2 years after the 1st dose is given. | Biological: TA-CIN (thigh)<br>* TA-CIN vaccine 100µg IM in the arm at Week 1, 5, and 9.<br>* Other names: Tissue Antigen - Cervical Intraepithelial Neoplasia;|
| Experimental: TA-CIN administration via arm<br>Each dose of TA-CIN vaccine is fixed, 100µg. Patients will receive 3 doses of the TA-CIN 4 weeks apart (Weeks 1, 5, and 9), administered in the arm. Patients will be followed for 2 years after the 1st dose is given. | Biological: TA-CIN (arm)<br>* TA-CIN vaccine 100µg IM in the arm at Week 1, 5, and 9.<br>* Other names: Tissue Antigen - Cervical Intraepithelial Neoplasia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and feasibility as assessed by Number of Participants with treatment-related Adverse Events | Safety and feasibility of intramuscular TA-CIN vaccine via arm or thigh as assessed by number of participants with with a history of HPV16 associated IB1-IV cervical cancer experiencing treatment-emergent adverse events as defined by CTCAE v4.0. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Response as measured by level of circulating antibody in peripheral blood | Level of circulating antibody to HPV16 E6, E7, and L2 in the peripheral blood pre- and post-vaccination (visualized by ELISA). | up to 4 years | 
| T-Cell Response as measured by level of circulating T-cells in peripheral blood | Level of circulating HPV16 E6- and E7- specific CD8+ T cells and/or CD4+ T cells in the peripheral blood pre- and post-vaccination (visualized by ELISPOT) | up to 4 years | 
| Mononucleocyte Response | Proliferative responses of peripheral blood mononucleocytes pre- and post-vaccination in response to stimulation by HPV16 E6, E7 and L2 | up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, HPV16, Cervical Cancer, TA-CIN, Vaccine, Adjuvant, Nickles FaderPI