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)
18 Years
N/A
Female
Cervical Cancer, Precancerous Condition
Trial Information
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)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety (according to NCI CTCAE v3.0) and tolerability
Outcome Time Frame:
12/31/2013
Safety Issue:
Yes
Principal Investigator
Cornelia L. Trimble, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
J0656 CDR0000617261
NCT ID:
NCT00788164
Start Date:
November 2008
Completion Date:
December 2015
Related Keywords:
- Cervical Cancer
- Precancerous Condition
- cervical cancer
- cervical intraepithelial neoplasia grade 3
- Uterine Cervical Neoplasms
- Precancerous Conditions
- Cervical Intraepithelial Neoplasia
- Carcinoma in Situ
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
