Vaccine Therapy With or Without Imiquimod in Treating Patients With Grade 3 Cervical Intraepithelial Neoplasia

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00788164
First received: November 7, 2008
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

RATIONALE: Vaccines made from 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 tumor cells from growing. Applying topical imiquimod to the cervix may be an effective treatment for cervical intraepithelial neoplasia. Giving vaccine therapy together with imiquimod may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy and to see how well it works when given with or without imiquimod in treating patients with grade 3 cervical intraepithelial neoplasia.


Condition Intervention Phase
Cervical Cancer
Precancerous Condition
Biological: TA-HPV
Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
Drug: imiquimod
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Efficacy and Safety Study of HPV16-specific Therapeutic DNA-vaccinia Vaccination in Combination With Topical Imiquimod, in Patients With HPV16+ High Grade Cervical Dysplasia (CIN3)

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety (according to NCI CTCAE v3.0) and tolerability [ Time Frame: 12/31/2014 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 28 [ Time Frame: 12/31/2014 ] [ Designated as safety issue: No ]
  • Quantitative changes in cervical HPV viral load in exfoliated cell samples [ Time Frame: 12/31/2014 ] [ Designated as safety issue: No ]
  • Changes in lesion size by serial digital colposcopy from week 0 to week 15 [ Time Frame: 12/31/2014 ] [ Designated as safety issue: No ]
  • Characterization of peripheral and local tissue response to vaccination on serially obtained peripheral blood specimens and on tissue samples from therapeutic resection [ Time Frame: 12/31/2014 ] [ Designated as safety issue: No ]
  • Correlation of immune response with clinical response [ Time Frame: 12/31/2014 ] [ Designated as safety issue: No ]
  • Correlation between measures of immune response and preclinical experimental data [ Time Frame: 12/31/2014 ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: November 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Groups 1-3
Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) on days 1 and 29 and TA-HPV vaccine IM on day 57.
Biological: TA-HPV
Given intramuscularly
Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
Given intramuscularly
Experimental: Group 4
Patients receive topical imiquimod on days 1, 29, and 57.
Drug: imiquimod
Given topically
Experimental: Group 5
Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV vaccine as in groups 1-3, and imiquimod as in group 4.
Biological: TA-HPV
Given intramuscularly
Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
Given intramuscularly
Drug: imiquimod
Given topically

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate safety, tolerability, and feasibility of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV vaccine with or without imiquimod in patients with human papillomavirus (HPV)16-positive grade 3 cervical intraepithelial neoplasia (CIN3).

Secondary

  • To evaluate the effect of this regimen on histology, based on the regression of cervical intraepithelial neoplasia.
  • To evaluate the feasibility and safety of study immunotherapy in these patients.
  • To evaluate the quantitative changes in cervical HPV viral load in these patients following study immunotherapy.
  • To evaluate changes in lesion size.
  • To evaluate the cellular and humoral immune response to vaccination.
  • To evaluate local tissue immune response.
  • To correlate measures of immune response with clinical response.
  • To correlate measures of immune response with those observed in the preclinical model.
  • 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 TA-HPV vaccine (groups 1-3 only). Patients are assigned to 1 of 5 treatment groups.

  • Groups 1-3: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) in weeks 0 and 4 and TA-HPV vaccine IM in week 8.
  • Group 4: Patients receive topical imiquimod applied to the cervix once in weeks 0, 4, and 8.
  • Group 5: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV vaccine as in groups 1-3, and imiquimod as in group 4.

Patients experiencing no improvement of their lesions at week 15 undergo standard cone resection of the squamocolumnar junction. If there is either 1) regression of the size of the lesions by colposcopy and/or 2) no CIN3 lesions detected by colposcopy/biopsy and Pap smear and/or 3) significant decrease of HPV viral load, patients are followed until week 28. At that time, loop electrosurgical excision procedure (LEEP) resection is performed if there is a CIN3 lesion detected by colposcopy/biopsy or suspected by Pap smear. Patients undergoing LEEP are followed until week 32. Patients not undergoing LEEP are followed until week 41 to confirm CIN3 regression.

Blood and tissue samples are collected periodically to measure immune response via ELISA, determine viral load and identify co-infecting HPV types via reverse-line blotting, and analyze lymphocytes via flow cytometry.

PROJECTED ACCRUAL: A total of 36 patients (3 in groups 1 and 2, 12 in groups 3 and 5, and 6 in group 4) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Colposcopically and biopsy confirmed grade 3 cervical intraepithelial neoplasia

    • Human papillomavirus (HPV) 16-positive disease by PCR
  • Measurable disease after diagnostic biopsy
  • No concurrent adenocarcinoma in situ of the cervix

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use an effective form of contraception during study treatment
  • Immunocompetent
  • No concurrent malignancy, except for nonmelanoma skin lesions
  • No serious concurrent disorder, including any of the following:

    • Active systemic infection
    • Autoimmune disease
    • Proven or suspected immunosuppressive disorder
    • Major medical illnesses of the cardiovascular or respiratory system
  • No evidence or history of cardiac disease, including any of the following:

    • Congestive heart failure
    • Symptomatic arrhythmia not controlled by medication
    • Unstable angina
    • History of acute myocardial infarction or cerebrovascular accident within the past 6 months
  • No history of severe allergy including eczema or other exfoliative skin disorder
  • No active eczema within the past 12 months
  • No concurrent skin conditions, including any of the following:

    • Burns
    • Traumatic or pruritic skin conditions
    • Open wounds
    • Unhealed surgical scars
  • Patients and their close social, sexual, or domestic contacts may not have any of the following active skin diseases:

    • Psoriasis
    • Lichen planus
    • Sever acneiform rash
    • Impetigo
    • Varicella zoster
    • Sepsis
  • No close social contact with children under 5 years old
  • No close social or domestic contact with a pregnant woman
  • No HIV seropositivity
  • No allergy to eggs

PRIOR CONCURRENT THERAPY:

  • No previous vaccination with vaccinia
  • No immunosuppressive medication (i.e., steroid therapy or other immunosuppressive/immunomodulating drugs [e.g., cyclosporine]) within the past 2 months
  • No investigational agent(s) within the past 6 months
  • No concurrent participation in another experimental protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00788164

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce    410-955-8804    jhcccro@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Cornelia L. Trimble, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00788164     History of Changes
Other Study ID Numbers: J0656 CDR0000617261, JHOC-J0656, NA_00002176, 2P50CA098252, 1R21CA123876
Study First Received: November 7, 2008
Last Updated: January 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
cervical cancer
cervical intraepithelial neoplasia grade 3

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Precancerous Conditions
Cervical Intraepithelial Neoplasia
Carcinoma in Situ
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on July 20, 2014