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Cervical CancerPhase 1NCT00788164

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

A Phase 1 study testing TA-HPV, pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and imiquimod in people with Cervical Cancer and Precancerous Condition, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
TA-HPV, pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and imiquimod
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteUnited States
Study dates
Nov 2008to Aug 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
TA-HPV, pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine, imiquimod
Keywords
cervical cancer, cervical intraepithelial neoplasia grade 3, therapeutic vaccine, treatment, CIN, HPV, vaccine, Hopkins, Trimble
Medical subject headings
Uterine Cervical Neoplasms, Precancerous Conditions, Uterine Cervical Dysplasia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TA-HPVBiological

    Given intramuscularly

  • pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccineBiological

    Given intramuscularly

  • imiquimodDrug

    Given topically

Study groups in NCT00788164
Study groupRoleWhat they receive
Groups 1-3ExperimentalPatients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine intramuscularly (IM) on days 1 and 29 and TA-HPV vaccine IM on day 57.
Receives: Biological: TA-HPV; Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
Group 4ExperimentalPatients receive topical imiquimod on days 1, 29, and 57.
Receives: Drug: imiquimod
Group 5ExperimentalPatients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV vaccine as in groups 1-3, and imiquimod as in group 4.
Receives: Biological: TA-HPV; Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine; Drug: imiquimod

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 10 weeks from the first intervention

Secondary outcomes (8)

  1. 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

    Measured: 15 weeks from the date of the first intervention

  2. Change in histology (CIN3 or no CIN3) of biopsies between baseline and week 28

    Absence of CIN3 as assessed by colposcopically directed biopsy at week 28.

    Measured: 28 weeks from the date of the first intervention

  3. Quantitative changes in cervical HPV viral load in exfoliated cell samples

    HPV genotypes present at study entry which become undetectable during the study window

    Measured: 41 weeks from the date of the first intervention

  4. 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

    Measured: Change from baseline to 15 weeks

  5. 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.

    Measured: Change from baseline to 15 weeks

  6. 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

    Measured: 41 weeks

  7. Correlation of immune response with clinical response

    Compare immune responses in the blood with histologic regression of CIN3 to CIN1 or less

    Measured: 41 weeks

  8. 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.

    Measured: 41 weeks from the date of the first study intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionAug 2023
  4. Study completionAug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00788164
Sponsor's protocol ID
J0656
Other IDs
NA_00002176, CDR0000617261, 2P50CA098252, 1R21CA123876
Status last verified
Aug 2023
First submitted
7 Nov 2008
Last updated
31 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 24477000

  • 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.

    PubMed 33468698

  • 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.

    PubMed 26420854

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TA-HPV, pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and imiquimod in people with Cervical Cancer and Precancerous Condition, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability as determined by number of participants with Serious Adverse Events (time frame: 10 weeks from the first intervention). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00788164, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.

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