We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00788164
Recruitment Status : Recruiting
First Posted : November 10, 2008
Last Update Posted : July 15, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Actual Study Start Date : November 2008
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines
Drug Information available for: Imiquimod

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Safety and tolerability as determined by number of participants with Serious Adverse Events [ Time Frame: 10 weeks from the first intervention ]
    Presence of Serious Adverse Events (as defined by according to NCI CTCAE v3.0) or dose limiting toxicities related to the study drugs.


Secondary Outcome Measures :
  1. Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 15 [ Time Frame: 15 weeks from the date of the first intervention ]
    Absence of CIN3 as assessed by colposcopically directed biopsy at week 15

  2. Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 28 [ Time Frame: 28 weeks from the date of the first intervention ]
    Absence of CIN3 as assessed by colposcopically directed biopsy at week 28.

  3. Quantitative changes in cervical HPV viral load in exfoliated cell samples [ Time Frame: 41 weeks from the date of the first intervention ]
    HPV genotypes present at study entry which become undetectable during the study window

  4. Change in number of lesions by serial digital colposcopy from week 0 to week 15 [ Time Frame: Change from baseline to 15 weeks ]
    Number of lesions that were present at baseline, then become undetectable by colposcopy at week 15

  5. Change in size of lesions by serial digital colposcopy from week 0 to week 15 [ Time Frame: Change from baseline to 15 weeks ]
    Change in size of lesions from baseline to week 15.

  6. Characterization of peripheral and local tissue response to vaccination [ Time Frame: 41 weeks ]
    Compare immune responses in the blood to local immune responses in the tissue for patients who receive the study intervention, from serially obtained peripheral blood specimens and on tissue samples from therapeutic resection

  7. Correlation of immune response with clinical response [ Time Frame: 41 weeks ]
    Compare immune responses in the blood with histologic regression of CIN3 to CIN1 or less

  8. Correlation between measures of immune response and preclinical experimental data [ Time Frame: 41 weeks from the date of the first study intervention ]
    Compare immune responses detected in patients who received the study intervention to those detected in the preclinical animal model.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00788164


Contacts
Layout table for location contacts
Contact: Maria Hom 410-502-0512 CervixDoctor@jhmi.edu

Locations
Layout table for location information
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 at Johns Hopkins
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Cornelia L. Trimble, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00788164    
Other Study ID Numbers: J0656
NA_00002176 ( Other Identifier: JHM IRB )
CDR0000617261 ( Other Identifier: other )
2P50CA098252 ( U.S. NIH Grant/Contract )
1R21CA123876 ( U.S. NIH Grant/Contract )
First Posted: November 10, 2008    Key Record Dates
Last Update Posted: July 15, 2022
Last Verified: July 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
cervical cancer
cervical intraepithelial neoplasia grade 3
therapeutic vaccine
treatment
CIN
 HPV
vaccine
Hopkins
Trimble
Additional relevant MeSH terms:
Layout table for MeSH terms
Uterine Cervical Neoplasms
Cervical Intraepithelial Neoplasia
Precancerous Conditions
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
 Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Interferon Inducers