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

June 20, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney kimmel comprehensive cancer center at johns hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed cervical intraepithelial neoplasia (CIN2/3)
  • Human papillomavirus-16-positive disease

PATIENT CHARACTERISTICS:

- Age: > 18

Other

  • Not pregnant
  • Immunocompetent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low dose

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
for the duration of the study, and whenever possible, for an additional 5 years
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.
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
Time Frame: 15 weeks
Number of participants with absence of CIN3 lesions at week 15
15 weeks
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)
41 weeks
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
9 months
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
9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Cornelia L. Trimble, MD, Sidney kimmel comprehensive cancer center at johns hopkins

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2003

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

July 19, 2005

First Submitted That Met QC Criteria

July 19, 2005

First Posted (Estimate)

July 21, 2005

Study Record Updates

Last Update Posted (Actual)

July 20, 2018

Last Update Submitted That Met QC Criteria

June 20, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J0323 CDR0000439494
  • P30CA006973 (U.S. NIH Grant/Contract)
  • R21CA105696 (U.S. NIH Grant/Contract)
  • JHOC-J0323
  • JHOC-03-05-06-02 (Other Identifier: JHM IRB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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