Vaccine Therapy With or Without Imiquimod in Treating Patients With Grade 3 Cervical Intraepithelial Neoplasia - Full Text View

Sponsors and Collaborators:	Johns Hopkins University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00788164

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/Nonmalignant Condition	Drug: TA-HPV Drug: imiquimod Drug: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: S 26308 PANVAC-V

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety (according to NCI CTCAE v3.0) and tolerability [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	36
Study Start Date:	October 2008
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Groups 1-3: Experimental Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) on days 1 and 29 and TA-HPV vaccine IM on day 57.	Drug: TA-HPV Given intramuscularly Drug: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine Given intramuscularly
Group 4: Experimental Patients receive topical imiquimod on days 1, 29, and 57.	Drug: imiquimod Given topically
Group 5: Experimental Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV vaccine as in groups 1-3, and imiquimod as in group 4.	Drug: TA-HPV Given intramuscularly Drug: imiquimod Given topically Drug: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine Given intramuscularly

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

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

Johns Hopkins University

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Cornelia L. Trimble, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Cornelia Liu Trimble )
Study ID Numbers:	CDR0000617261, JHOC-J0656, NA_00002176
Study First Received:	November 7, 2008
Last Updated:	November 12, 2008
ClinicalTrials.gov Identifier:	NCT00788164
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

cervical cancer
cervical intraepithelial neoplasia grade 3

Study placed in the following topic categories:

Precancerous Conditions
Vaccinia
Cervical intraepithelial neoplasia
Carcinoma in Situ
Interferons

Imiquimod
Uterine Cervical Dysplasia
Neoplasms, Glandular and Epithelial
Carcinoma
Cervical Intraepithelial Neoplasia

Additional relevant MeSH terms:

Interferon Inducers
Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Antineoplastic Agents

Therapeutic Uses
Physiological Effects of Drugs
Adjuvants, Immunologic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009