Vaccine Therapy With or Without Imiquimod in Treating Patients With Grade 3 Cervical Intraepithelial Neoplasia

NCT00788164 | Completed Phase 1 DMC FDA Drug

• 5 other identifiers: J0656NA_00002176CDR00006172612P50CA0982521R21CA123876
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cervical Cancer; Precancerous Condition; HPV Disease; Human Papilomavirus

Keywords

cervical cancer; cervical intraepithelial neoplasia grade 3; therapeutic vaccine; treatment; CIN; HPV; vaccine; Hopkins; Trimble

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Change in histology (CIN3 or no CIN3) of biopsies between baseline and 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

  28 weeks from the date of the first intervention

• Quantitative changes in cervical HPV viral load in exfoliated cell samples

  41 weeks from the date of the first intervention

• Change in number of lesions by serial digital colposcopy from week 0 to week 15

  Change from baseline to 15 weeks

• Change in size of lesions by serial digital colposcopy from week 0 to week 15

  Change from baseline to 15 weeks

Study Arms (3)

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.

Biological: TA-HPV; Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine

Group 4

EXPERIMENTAL

Patients receive topical imiquimod on days 1, 29, and 57.

Drug: imiquimod

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.

Biological: TA-HPV; Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine; Drug: imiquimod

Interventions

TA-HPV BIOLOGICAL

Given intramuscularly

Group 5; Groups 1-3

pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine BIOLOGICAL

Given intramuscularly

Group 5; Groups 1-3

imiquimod DRUG

Given topically

Group 4; Group 5

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (3)

• 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.

  PMID: 24477000 RESULT

• 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.

  PMID: 33468698 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.

  PMID: 26420854 DERIVED

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Precancerous Conditions; Uterine Cervical Dysplasia

Interventions

human papillomavirus vaccine, TA; Imiquimod

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Cornelia L. Trimble, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2008
• First Posted: November 10, 2008
• Study Start: November 1, 2008
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: August 31, 2023

Record last verified: 2023-08

Locations

US (1)