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

Overview

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 2010

Detailed Description

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.

Interventions

  • Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
    • recombinant DNA vaccine

Arms, Groups and Cohorts

  • Experimental: Low dose
    • 3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals. Genetic (recombinant DNA vaccine)
  • Experimental: Intermediate dose
    • 3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine)
  • Experimental: High dose
    • 3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine)

Clinical Trial Outcome Measures

Primary Measures

  • Safety and Toxicity
    • Time Frame: for the duration of the study, and whenever possible, for an additional 5 years
    • Number of participants with serious adverse events (SAE) according to CTCAE 3.0 grading.
  • Efficacy
    • Time Frame: for the duration of the study, and whenever possible, for an additional 5 years
    • 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.

Secondary Measures

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

Participating in This Clinical Trial

DISEASE CHARACTERISTICS:

  • Histologically confirmed cervical intraepithelial neoplasia (CIN2/3) – Human papillomavirus-16-positive disease PATIENT CHARACTERISTICS: – Age: > 18 Other – Not pregnant – Immunocompetent
  • Gender Eligibility: Female

    Minimum Age: 18 Years

    Maximum Age: 120 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Collaborator
      • National Cancer Institute (NCI)
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Cornelia L. Trimble, MD, Study Chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Citations Reporting on Results

    Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, Pardoll D, Wu TC. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009 Jan 1;15(1):361-7. doi: 10.1158/1078-0432.CCR-08-1725.

    Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

    At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.