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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00002176 | Other Identifier | JHM IRB | |
| CDR0000617261 | Other Identifier | other | |
| 2P50CA098252 | U.S. NIH Grant/Contract | View source | |
| 1R21CA123876 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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
Secondary
OUTLINE: This is a dose escalation study of TA-HPV vaccine (groups 1-3 only). Patients are assigned to 1 of 5 treatment groups.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Group 4 | Experimental | Patients receive topical imiquimod on days 1, 29, and 57. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TA-HPV | Biological | Given intramuscularly |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability as determined by number of participants with Serious Adverse Events | Presence of Serious Adverse Events (as defined by according to NCI CTCAE v3.0) or dose limiting toxicities related to the study drugs. | 10 weeks from the first intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 15 | Absence of CIN3 as assessed by colposcopically directed biopsy at week 15 | 15 weeks from the date of the first intervention |
| Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 28 |
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DISEASE CHARACTERISTICS:
Colposcopically and biopsy confirmed grade 3 cervical intraepithelial neoplasia
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:
No evidence or history of cardiac disease, including any of the following:
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:
Patients and their close social, sexual, or domestic contacts may not have any of the following active skin diseases:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Cornelia L. Trimble, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231-2410 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24477000 | Result | Maldonado L, Teague JE, Morrow MP, Jotova I, Wu TC, Wang C, Desmarais C, Boyer JD, Tycko B, Robins HS, Clark RA, Trimble CL. Intramuscular therapeutic vaccination targeting HPV16 induces T cell responses that localize in mucosal lesions. Sci Transl Med. 2014 Jan 29;6(221):221ra13. doi: 10.1126/scitranslmed.3007323. | |
| 33468698 | Derived | Peng S, Ferrall L, Gaillard S, Wang C, Chi WY, Huang CH, Roden RBS, Wu TC, Chang YN, Hung CF. Development of DNA Vaccine Targeting E6 and E7 Proteins of Human Papillomavirus 16 (HPV16) and HPV18 for Immunotherapy in Combination with Recombinant Vaccinia Boost and PD-1 Antibody. mBio. 2021 Jan 19;12(1):e03224-20. doi: 10.1128/mBio.03224-20. |
| Label | URL |
|---|---|
| Clinical trial summary from the National Cancer Institute's PDQ® database | View source |
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| pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine |
| Biological |
Given intramuscularly |
|
| imiquimod | Drug | Given topically |
|
Absence of CIN3 as assessed by colposcopically directed biopsy at week 28. |
| 28 weeks from the date of the first intervention |
| Quantitative changes in cervical HPV viral load in exfoliated cell samples | HPV genotypes present at study entry which become undetectable during the study window | 41 weeks from the date of the first intervention |
| Change in number of lesions by serial digital colposcopy from week 0 to week 15 | Number of lesions that were present at baseline, then become undetectable by colposcopy at week 15 | Change from baseline to 15 weeks |
| Change in size of lesions by serial digital colposcopy from week 0 to week 15 | Change in size of lesions from baseline to week 15. | Change from baseline to 15 weeks |
| Characterization of peripheral and local tissue response to vaccination | 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 | 41 weeks |
| Correlation of immune response with clinical response | Compare immune responses in the blood with histologic regression of CIN3 to CIN1 or less | 41 weeks |
| Correlation between measures of immune response and preclinical experimental data | Compare immune responses detected in patients who received the study intervention to those detected in the preclinical animal model. | 41 weeks from the date of the first study intervention |
| 26420854 | Derived | Sun YY, Peng S, Han L, Qiu J, Song L, Tsai Y, Yang B, Roden RB, Trimble CL, Hung CF, Wu TC. Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract. Clin Cancer Res. 2016 Feb 1;22(3):657-69. doi: 10.1158/1078-0432.CCR-15-0234. Epub 2015 Sep 29. |
| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| D011230 | Precancerous Conditions |
| D002578 | Uterine Cervical Dysplasia |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| C100344 | human papillomavirus vaccine, TA |
| D000077271 | Imiquimod |
| ID | Term |
|---|---|
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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