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

Cervical Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00121173
• Other study ID #: J0323 CDR0000439494
• Secondary ID: R21CA105696P30CA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2003
• Est. completion date: January 2010

Study information

• Verified date: June 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed cervical intraepithelial neoplasia (CIN2/3)

• Human papillomavirus-16-positive disease

PATIENT CHARACTERISTICS:

• Age: > 18

Other

• Not pregnant

• Immunocompetent

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Cancer
• Cervical Intraepithelial Neoplasia
• Neoplasms
• Precancerous Condition
• Precancerous Conditions
• Uterine Cervical Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-08-172 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Regression of CIN3 Lesions	Number of participants with absence of CIN3 lesions at week 15	15 weeks
Secondary	Number of Participants With T-cell Immune Responses in the Blood	Systemic T-cell response as measured by ?-INF enzyme-linked immunospot assays (ELISpot)	41 weeks
Secondary	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
Secondary	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

External Links

•   Publication of study results in Clin Cancer Res