Clinical trial NCT00121173: Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia
Official title: 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: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Precancerous Condition
Keywords: cervical cancer
cervical intraepithelial neoplasia grade 2
cervical intraepithelial neoplasia grade 3
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-07-21
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

- Age: \> 18

Other

* Not pregnant
* Immunocompetent

Primary outcomes:
measure: Safety and Toxicity
timeFrame: for the duration of the study, and whenever possible, for an additional 5 years
measure: Efficacy
timeFrame: for the duration of the study, and whenever possible, for an additional 5 years
Secondary outcomes:
measure: Regression of CIN3 Lesions
timeFrame: 15 weeks
measure: Number of Participants With T-cell Immune Responses in the Blood
timeFrame: 41 weeks
measure: Number of Participants With Correlated Measures of Immune Response With Clinical Response
timeFrame: 9 months
measure: Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model
timeFrame: 9 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Cornelia L. Trimble, MD
role: STUDY_CHAIR
References:
citation: 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.