Vaccine Therapy with or without Imiquimod in Treating Patients with High-Grade Cervical Intraepithelial Neoplasia

Status: Active

Description

This pilot phase I trial studies the side effects and best dose of giving vaccine therapy with or without imiquimod in treating patients with high-grade cervical intraepithelial neoplasia. Vaccines made from deoxyribonucleic acid (DNA) or a gene-modified virus may help the body build an effective immune response to kill tumor cells. Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop cancer cells from growing. Giving vaccine therapy together with imiquimod may be a better treatment for cervical intraepithelial neoplasia.

Eligibility Criteria

Inclusion Criteria

  • Patients with high-grade cervical intraepithelial lesions (CIN2/3) confirmed by colposcopy, biopsy, and review of the biopsy pathology slides by two pathologists
  • Patients whose lesions are HPV16+ by polymerase chain reaction (PCR) (treatment groups 1, 2, 3 and 5); group 4 (imiquimod alone: 12 HPV16+ subjects, 36 HPV16- subjects)
  • Patients who have measurable disease after diagnostic biopsy
  • An approved informed consent and authorization permitting release of personal health information must be signed by the patient or guardian
  • Patients who are immunocompetent
  • Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception during the study

Exclusion Criteria

  • Patients with evidence of concurrent adenocarcinoma-in-situ
  • Patients with serious, concomitant disorder, including active systemic infection, autoimmune disease, proven or suspected immunosuppressive disorder or any other major medical illnesses of the cardiovascular or respiratory system, concurrent malignancy except for nonmelanoma skin lesions
  • Patients who are human immunodeficiency virus (HIV) seropositive
  • Patients who take immunosuppressive medication, i.e. steroid therapy or other immunosuppressive/immunomodulating drugs (e.g. Cyclosporine) within 2 months prior to first study drug injection
  • Patients who are pregnant, planning pregnancy, or breast feeding
  • Patients who are participating in another experimental protocol during the study period (last intake of investigational drug within 6 months prior to first study drug injection)
  • SUBJECTS ENROLLED IN THE TREATMENT GROUPS RECEIVING VACCINE ONLY (NOT THE IMIQUIMOD GROUP):
  • Patients with a history of severe allergy including eczema or other exfoliative skin disorder or active skin diseases such as psoriasis, lichen planus, severe acneiform rash, impetigo, varicella zoster, or sepsis among patients or among close social, sexual or domestic contacts; patients with burns or other traumatic or pruritic skin conditions or open wounds should not receive the vaccine until the condition has resolved; surgical scars must be healed
  • Patients with active eczema during the last 12 months
  • Patients who have an allergy to eggs
  • Patients who are in close social contact with children under 5 years old
  • Patients who are in close social/domestic contact with a pregnant woman
  • Patients who have been previously vaccinated with vaccinia
  • Patients with evidence/history of cardiac disease including congestive heart failure, symptomatic arrhythmia not controlled by medication, unstable angina or cardiac disease, history of acute myocardial infarction (MI) or cerebrovascular accident (CVA) within the past six months

Locations & Contacts

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Cornelia Liu Trimble
Phone: 410-502-0512
Email: ctrimbl@jhmi.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate safety, tolerability, and feasibility of pNGVL4a-Sig/E7(detox)/heat shock protein (HSP)70 DNA vaccine and human papillomavirus tumor antigen vaccine (TA-HPV) (DNA-DNA-TA-HPV) vaccination in patients with human papillomavirus (HPV)16+ cervical intraepithelial neoplasia (CIN)2/3, with and without topical adjuvant.

SECONDARY OBJECTIVES:

I. To evaluate the effect of vaccination on histology, based on the regression of CIN2/3 at week 28, assessed as either CIN1 or no CIN lesion detected by colposcopy/biopsy and Pap smear.

II. To evaluate the feasibility and safety of study immunotherapy in patients with HPV16+ CIN2/3.

III. To evaluate the quantitative changes in cervical HPV viral load in these patients following study immunotherapy.

IV. To evaluate changes in lesion size.

V. To evaluate the cellular and humoral immune responses to vaccination.

VI. To evaluate local tissue immune response.

VII. To correlate measures of immune response with clinical response.

VIII. To correlate measures of immune response with those observed in the preclinical model.

IX. To evaluate if the efficacy of the prime-boost vaccination can be improved with the cervical application of imiquimod.

OUTLINE: This is a dose-escalation study of human papillomavirus tumor antigen vaccine (groups 1-3 only). Patients are sequentially assigned to 1 of 5 treatment groups.

GROUPS I-III: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) in weeks 0 and 4 and human papillomavirus tumor antigen vaccine IM in week 8.

GROUP IV: Patients receive topical imiquimod in weeks 0, 4, and 8.

GROUP V: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine IM and human papillomavirus tumor antigen vaccine IM as in Groups I-III. Patients also receive topical imiquimod as in Group IV.

In all groups, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Prevention

Lead Organization

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Cornelia Liu Trimble

Trial IDs

Primary ID J0656
Secondary IDs NCI-2011-00532, NA_00002176, JHOC-J0656, CIR00001225, CDR0000617261
Clinicaltrials.gov ID NCT00788164