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

Phase 1

Completed

• Conditions: Cervical Cancer; Precancerous Condition
• Interventions: Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine

• Registration Number: NCT00121173
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

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

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 Timeline

• Study Start: 2003-11
• Study First Submitted: 2005-07-19
• Study First Submitted QC: 2005-07-19
• Study First Posted: 2005-07-21
• Primary Completion: 2010-01
• Study Completion: 2010-01
• Results First Submitted: 2014-03-28
• Status Verified: 2018-06
• Results First Submitted QC: 2018-06-20
• Last Update Submitted: 2018-06-20
• Results First Posted: 2018-07-20
• Last Update Posted: 2018-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Safety and Toxicity	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	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 Outcome Measures

Name	Time	Method
Regression of CIN3 Lesions	15 weeks	Number of participants with absence of CIN3 lesions at week 15
Number of Participants With T-cell Immune Responses in the Blood	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	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	9 months	Number of participants whose T-cell immune responses correlated with the immune responses observed in the preclinical model

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States