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 August 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: August 6, 2014
Last verified: August 2014

November 7, 2008
August 6, 2014
November 2008
December 2015   (final data collection date for primary outcome measure)
Safety (according to NCI CTCAE v3.0) and tolerability [ Time Frame: 12/31/2014 ] [ Designated as safety issue: Yes ]
Safety (according to NCI CTCAE v3.0) and tolerability [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00788164 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 28 [ Designated as safety issue: No ]
  • Quantitative changes in cervical HPV viral load in exfoliated cell samples [ Designated as safety issue: No ]
  • Changes in lesion size by serial digital colposcopy from week 0 to week 15 [ 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 [ Designated as safety issue: No ]
  • Correlation of immune response with clinical response [ Designated as safety issue: No ]
  • Correlation between measures of immune response and preclinical experimental data [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vaccine Therapy With or Without Imiquimod in Treating Patients With Grade 3 Cervical Intraepithelial Neoplasia
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)

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cervical Cancer
  • Precancerous Condition
  • Biological: TA-HPV
    Given intramuscularly
  • Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
    Given intramuscularly
  • Drug: imiquimod
    Given topically
  • 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.
    Interventions:
    • Biological: TA-HPV
    • Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
  • Experimental: Group 4
    Patients receive topical imiquimod on days 1, 29, and 57.
    Intervention: Drug: imiquimod
  • 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.
    Interventions:
    • Biological: TA-HPV
    • Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
    • Drug: imiquimod
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
48
July 2016
December 2015   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
United States
 
NCT00788164
J0656 CDR0000617261, JHOC-J0656, NA_00002176, 2P50CA098252, 1R21CA123876
Yes
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Cornelia L. Trimble, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP