Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from protein and DNA may help the body build an effective immune response to kill abnormal cells in the cervix. The use of vaccine therapy may prevent cervical cancer. PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy and to see how well it works in preventing cervical cancer in patients with cervical intraepithelial neoplasia and human papillomavirus.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility and toxicity of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine in preventing cervical cancer in patients with human papillomavirus (HPV)-16-positive grade 2 or 3 cervical intraepithelial neoplasia. Determine the effect of this vaccine on the histology of cervical tissue specimens from these patients. Secondary Determine changes in lesion size and HPV viral load in patients treated with this vaccine. Determine the cellular, humoral, and local tissue immune responses in patients treated with this vaccine. Correlate measures of immune response with clinical response in patients treated with this vaccine. Correlate measures of immune response in patients treated with this vaccine with those observed in the preclinical model. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Phase I: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine subcutaneously once in weeks 0, 4, and 8 in the absence of disease progression or unacceptable toxicity. Patients undergo colposcopy in week 8, 15 and 19 and a therapeutic loop electrosurgical excision procedure (LEEP) in week 15. Cohorts of patients receive escalating doses of vaccine until the safest dose is determined. Phase II: Patients receive vaccine as in phase I but at the safest dose determined in phase I. Patients also undergo colposcopy and LEEP as in phase I. After completion of the study treatment, patients are followed annually for 15 years. PROJECTED ACCRUAL: Approximately 150 patients (approximately 12 will be treated in phase I and 25 will be treated in phase II) will be accrued for this study.

Official Title
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A Phase I/II Clinical Trial of pNGVL4a-Sig/E7 (Detox)/HSP70 for the Treatment of Patients With HPV 16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)

Conditions
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Cervical Cancer, Precancerous Condition

Intervention / Treatment
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* Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cervical intraepithelial neoplasia (CIN2/3) Human papillomavirus-16-positive disease PATIENT CHARACTERISTICS: - Age: > 18 Other Not pregnant Immunocompetent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals. Genetic (recombinant DNA vaccine) | Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine<br>* recombinant DNA vaccine<br>|
| Experimental: Intermediate dose<br>3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine) | Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine<br>* recombinant DNA vaccine<br>|
| Experimental: High dose<br>3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine) | Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine<br>* recombinant DNA vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Toxicity | Number of participants with serious adverse events (SAE) according to CTCAE 3.0 grading. | for the duration of the study, and whenever possible, for an additional 5 years | 
| Efficacy | The efficacy of pNGVL4a-SigE7(detox)HSP70 DNA vaccine, administered intra-muscularly. This is reported as number of participants with histologic regression of CIN2/3 to CIN1 or less by colposcopically-directed biopsy. | for the duration of the study, and whenever possible, for an additional 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regression of CIN3 Lesions | Number of participants with absence of CIN3 lesions at week 15 | 15 weeks | 
| Number of Participants With T-cell Immune Responses in the Blood | Systemic T-cell response as measured by γ-INF enzyme-linked immunospot assays (ELISpot) | 41 weeks | 
| Number of Participants With Correlated Measures of Immune Response With Clinical Response | Number of participants whose t-cell immune responses correlated with histologic regression of disease or viral clearance of HPV | 9 months | 
| Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model | Number of participants whose T-cell immune responses correlated with the immune responses observed in the preclinical model | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 3