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

NCT ID: NCT00121173

Last Updated: 2018-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30
• Study Completion Date: 2010-01-31

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.

Conditions

Cervical Cancer; Precancerous Condition

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Low dose

3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals.

Genetic (recombinant DNA vaccine)

Group Type: EXPERIMENTAL

pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine

Intervention Type: BIOLOGICAL

recombinant DNA vaccine

Intermediate dose

3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine)

Group Type: EXPERIMENTAL

pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine

Intervention Type: BIOLOGICAL

recombinant DNA vaccine

High dose

3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine)

Group Type: EXPERIMENTAL

pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine

Intervention Type: BIOLOGICAL

recombinant DNA vaccine

Interventions

pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine

recombinant DNA vaccine

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

• Age: > 18

Other

• Not pregnant
• Immunocompetent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelia L. Trimble, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 19118066 (View on PubMed)

Other Identifiers

R21CA105696

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0323

Identifier Type: -

Identifier Source: secondary_id

JHOC-03-05-06-02

Identifier Type: OTHER

Identifier Source: secondary_id

J0323 CDR0000439494

Identifier Type: -

Identifier Source: org_study_id