Safety and Tolerability Evaluation Study of BVAC-C in Patients With HPV Type 16 or 18 Positive Cervical Cancer

Study Overview
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Brief Summary
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BVAC-C is an immunotherapeutic vaccine using B-Cell and Monocytes as antigen-presenting cells. This study is consists of 2 parts. Phase I is for safety evaluation, and Phase IIa is for efficacy assessment.

Detailed Description
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BVAC-C is an immunotherapeutic vaccine using B-Cell and Monocytes as antigen-presenting cells. This study is consists of 2 parts(Phase I, Phase II). Phase I study is Open-label, dose-escalation, multiple dosing study to evaluate the safety, tolerability, immune response and preliminary efficacy of BVAC-C in patients with multiple metastatic progressive or recurrent HPV type 16 or 18 positive cervical cancer after failure to standard care. 9 18 patients will be enrolled In Phase IIa study, which Open-label, sequential assignment multiple dosing study, efficacy, immune response and safety will be evaluated. Total 21 patients will be enrolled in 3 groups.

Official Title
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Open-label, Dose-escalation, Multiple Dosing Study to Evaluate the Safety, Tolerability, Immune Response and Pre Efficacy of BVAC-C in Patients With Multiple Metastatic Progressive or Recurrent HPV Type 16 or 18 Positive Cervical Cancer After Failure to Standard Care

Conditions
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Uterine Cervical Neoplasms

Intervention / Treatment
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* Drug: BVAC-C
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with multiple metastatic progressive or recurrent HPV type 16 or 18 positive cervical cancer Patients has received 1 or more platinum based doublet chemotherapy as prior therapy for progressive or recurrent tumor lesion (prior therapy does not include platinum chemotherapy given with radiation therapy for 1st line treatment before progression or recurrence) Patients with at least 1 measurable lesion according to RECIST Female patients between ages of 20 to 70 Patients with ECOG performance status between 0 to 2 Patients meets the blood test standards in the screening test ANC≥1500/μL LLN ≤ALC ≤ULN Platelets≥100,000/μL Hemoglobin> 9g/dL Patients meets the blood chemistry test standards in the screening test Serum creatinine ≤ 2.0 mg/dL Calculated creatinine clearance ≥ 50 mL/min Serum bilirubin ≤1.5 x ULN ALT and AST ≤2.5 × ULN (≤ 5 x ULN in patients with liver metastases) Patients who has agreed to a medically accepted contraceptive in this clinical trial Patients at least three months or more of survival can be expected Patients decided to participate in this clinical trial and signed written informed consent Exclusion Criteria: Patients histopathology is a neuroendocrine or small cell carcinoma Patients with a history of brain metastasis or signs of brain metastasis Patients tested positive in serological tests for hepatitis C virus or hepatitis B virus surface antigen, (HBsAg) or human immunodeficiency virus (HIV) Patients with a history of HIV infection Patients showing abnormal electrocardiogram , including arrhythmia Patients have been administered the drug for other clinical trials within 4weeks before the screening visit Patients have been administered any vaccines within 4weeks before the screening visit (eg. hepatitis A, hepatitis B, influenza, Td, etc. ) Patients have been administered the blood products within 3 months before the screening visit Patients have received chemotherapy or radiation therapy within 4weeks before the 1st administration of investigational drug (BVAC-C) Patients treated with immunosuppressant or immunomodulatory agents within 6 months before the screening visit Patients who have participated in the clinical trial of a therapeutic vaccine or immune therapy within 1 year before the screening visit Patients with a history of serious allergic disease or serious side effects of the drug Patients who is pregnant or breast-feeding Patients researchers has determined that participation in the clinical trial is inappropriate Patients suspected to have other primary cancer

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BVAC-C mono(High dose)<br>BVAC-C IV injection at 0, 4, 8th weeks.(HIgh dose) | Drug: BVAC-C<br>* Autologous B cells and monocytes transfected with E6E7 gene of HPV<br>|
| Experimental: BVAC-C mono(Intermediate dose)<br>BVAC-C IV injection at 0, 4, 8, 12th weeks.(Half dose) | Drug: BVAC-C<br>* Autologous B cells and monocytes transfected with E6E7 gene of HPV<br>|
| Experimental: BVAC-C + Topo Combi<br>BVAC-C IV injection at 0,4,8,12th weeks.(Half dose) Topotecan IV injection at 2, 6, 10, 14th weeks | Drug: BVAC-C<br>* Autologous B cells and monocytes transfected with E6E7 gene of HPV<br>Drug: Topotecan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate DLT with Clinical laboratory tests [Safety] | Lymphocyte subset, Serum cytokine, NKT/NK cell assay, CD4/CD8 assay | 12th week from first injection (End of trial) | 
| Incidence of Serious Adverse Events assessed with CTCAE [Safety] |  | 12th week from first injection (End of trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical laboratory tests | Blood chemistry, Serology | Screening visit and every 2 weeks from first injection (up to 12th week) | 
| 12-lead ECG |  | Screening visit and Termination visit (12th week from first injection) | 
| Vital signs | Blood pressure, Pulse rate, Respiratory rate, Tympanic temperature | Every 2 weeks from first injection (up to 12th week) | 
| Physical examination | Body weight | Screening, 6th week from first injection, 10th week from first injection and Termination visit (12th week from first injection) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Type 16, 18, E6E7, Immune therapeutic vaccine