Vaccine Therapy With or Without Imiquimod in Treating Patients With Grade 3 Cervical Intraepithelial Neoplasia
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|ClinicalTrials.gov Identifier: NCT00788164|
Recruitment Status : Recruiting
First Posted : November 10, 2008
Last Update Posted : October 9, 2018
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|
- 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).
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (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)|
|Actual Study Start Date :||November 2008|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||June 2020|
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: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
Experimental: Group 4
Patients receive topical imiquimod on days 1, 29, and 57.
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: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
- 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.
- 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
- 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.
- 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
- 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
- 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.
- 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
- 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
- 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.
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
|Contact: Maria Homemail@example.com|
|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 firstname.lastname@example.org|
|Principal Investigator:||Cornelia L. Trimble, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|