Cervical CancerPhase 1/2NCT00121173
Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia
A Phase 1/2 study testing pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine in people with Cervical Cancer and Precancerous Condition, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
RATIONALE: Vaccines made from protein and DNA may help the body build an effective immune response to kill abnormal cells in the cervix. The use of vaccine therapy may prevent cervical cancer. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Cervical Cancer, Precancerous Condition
- What is being tested?
- pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2003to Jan 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed cervical intraepithelial neoplasia (CIN2/3)
- Human papillomavirus-16-positive disease
PATIENT CHARACTERISTICS:
- Age: > 18
Other
- Not pregnant
- Immunocompetent
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
About this study
Official title: A Phase I/II Clinical Trial of pNGVL4a-Sig/E7 (Detox)/HSP70 for the Treatment of Patients With HPV 16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)
RATIONALE: Vaccines made from protein and DNA may help the body build an effective immune response to kill abnormal cells in the cervix. The use of vaccine therapy may prevent cervical cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy and to see how well it works in preventing cervical cancer in patients with cervical intraepithelial neoplasia and human papillomavirus.
Read the detailed description
OBJECTIVES:
Primary
- Determine the feasibility and toxicity of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine in preventing cervical cancer in patients with human papillomavirus (HPV)-16-positive grade 2 or 3 cervical intraepithelial neoplasia.
- Determine the effect of this vaccine on the histology of cervical tissue specimens from these patients.
Secondary
- Determine changes in lesion size and HPV viral load in patients treated with this vaccine.
- Determine the cellular, humoral, and local tissue immune responses in patients treated with this vaccine.
- Correlate measures of immune response with clinical response in patients treated with this vaccine.
- Correlate measures of immune response in patients treated with this vaccine with those observed in the preclinical model.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine subcutaneously once in weeks 0, 4, and 8 in the absence of disease progression or unacceptable toxicity. Patients undergo colposcopy in week 8, 15 and 19 and a therapeutic loop electrosurgical excision procedure (LEEP) in week 15.
Cohorts of patients receive escalating doses of vaccine until the safest dose is determined.
- Phase II: Patients receive vaccine as in phase I but at the safest dose determined in phase I. Patients also undergo colposcopy and LEEP as in phase I.
After completion of the study treatment, patients are followed annually for 15 years.
PROJECTED ACCRUAL: Approximately 150 patients (approximately 12 will be treated in phase I and 25 will be treated in phase II) will be accrued for this study.
- Conditions
- Cervical Cancer, Precancerous Condition
- Being tested
- pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
- Keywords
- cervical cancer, cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 3
- 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.
pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccineBiological
recombinant DNA vaccine
| Study group | Role | What they receive |
|---|---|---|
| Low dose | Experimental | 3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals.
Genetic (recombinant DNA vaccine) Receives: Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine |
| Intermediate dose | Experimental | 3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine) Receives: Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine |
| High dose | Experimental | 3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine) Receives: Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Toxicity
Number of participants with serious adverse events (SAE) according to CTCAE 3.0 grading.
Measured: for the duration of the study, and whenever possible, for an additional 5 years
Efficacy
The efficacy of pNGVL4a-SigE7(detox)HSP70 DNA vaccine, administered intra-muscularly. This is reported as number of participants with histologic regression of CIN2/3 to CIN1 or less by colposcopically-directed biopsy.
Measured: for the duration of the study, and whenever possible, for an additional 5 years
Secondary outcomes (4)
Regression of CIN3 Lesions
Number of participants with absence of CIN3 lesions at week 15
Measured: 15 weeks
Number of Participants With T-cell Immune Responses in the Blood
Systemic T-cell response as measured by γ-INF enzyme-linked immunospot assays (ELISpot)
Measured: 41 weeks
Number of Participants With Correlated Measures of Immune Response With Clinical Response
Number of participants whose t-cell immune responses correlated with histologic regression of disease or viral clearance of HPV
Measured: 9 months
Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model
Number of participants whose T-cell immune responses correlated with the immune responses observed in the preclinical model
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2005 (estimated)
- Study startNov 2003
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Cornelia L. Trimble, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00121173
- Sponsor's protocol ID
- J0323 CDR0000439494
- Other IDs
- R21CA105696, P30CA006973, JHOC-J0323, JHOC-03-05-06-02
- Status last verified
- Jun 2018
- First submitted
- 19 Jul 2005
- Last updated
- 20 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, Pardoll D, Wu TC. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009 Jan 1;15(1):361-7. doi: 10.1158/1078-0432.CCR-08-1725.
PubMed 19118066
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial of pNGVL4a-Sig/E7 (Detox)/HSP70 for the Treatment of Patients With HPV 16+ Cervical Intraepithelial Neoplasia 2/3 (CIN2/3)
- ClinicalTrials.gov ID
- NCT00121173
- Acronym / sponsor ID
- J0323 CDR0000439494
- Conditions
- Cervical Cancer, Precancerous Condition
- Keywords
- cervical cancer, cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 3
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2003
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 21 Jul 2005 (estimated)
- Results
- Posted 20 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Vaccines made from protein and DNA may help the body build an effective immune response to kill abnormal cells in the cervix. The use of vaccine therapy may prevent cervical cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy and to see how well it works in preventing cervical cancer in patients with cervical intraepithelial neoplasia and human papillomavirus.
Detailed description
OBJECTIVES:
Primary
- Determine the feasibility and toxicity of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine in preventing cervical cancer in patients with human papillomavirus (HPV)-16-positive grade 2 or 3 cervical intraepithelial neoplasia.
- Determine the effect of this vaccine on the histology of cervical tissue specimens from these patients.
Secondary
- Determine changes in lesion size and HPV viral load in patients treated with this vaccine.
- Determine the cellular, humoral, and local tissue immune responses in patients treated with this vaccine.
- Correlate measures of immune response with clinical response in patients treated with this vaccine.
- Correlate measures of immune response in patients treated with this vaccine with those observed in the preclinical model.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine subcutaneously once in weeks 0, 4, and 8 in the absence of disease progression or unacceptable toxicity. Patients undergo colposcopy in week 8, 15 and 19 and a therapeutic loop electrosurgical excision procedure (LEEP) in week 15.
Cohorts of patients receive escalating doses of vaccine until the safest dose is determined.
- Phase II: Patients receive vaccine as in phase I but at the safest dose determined in phase I. Patients also undergo colposcopy and LEEP as in phase I.
After completion of the study treatment, patients are followed annually for 15 years.
PROJECTED ACCRUAL: Approximately 150 patients (approximately 12 will be treated in phase I and 25 will be treated in phase II) will be accrued for this study.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low dose | Experimental | Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals. Genetic (recombinant DNA vaccine) |
| Intermediate dose | Experimental | Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine) |
| High dose | Experimental | Biological: pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM at one month intervals Genetic (recombinant DNA vaccine) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccinerecombinant DNA vaccine | Biological | High dose, Intermediate dose, Low dose |
Primary outcome
Safety and Toxicity
Time frame: for the duration of the study, and whenever possible, for an additional 5 years
Number of participants with serious adverse events (SAE) according to CTCAE 3.0 grading.
Efficacy
Time frame: for the duration of the study, and whenever possible, for an additional 5 years
The efficacy of pNGVL4a-SigE7(detox)HSP70 DNA vaccine, administered intra-muscularly. This is reported as number of participants with histologic regression of CIN2/3 to CIN1 or less by colposcopically-directed biopsy.
4 secondary outcomes
Regression of CIN3 Lesions
Time frame: 15 weeks
Number of Participants With T-cell Immune Responses in the Blood
Time frame: 41 weeks
Number of Participants With Correlated Measures of Immune Response With Clinical Response
Time frame: 9 months
Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model
Time frame: 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19118066Trimble CL, Peng S, Kos F, Gravitt P, Viscidi R, Sugar E, Pardoll D, Wu TC. A phase I trial of a human papillomavirus DNA vaccine for HPV16+ cervical intraepithelial neoplasia 2/3. Clin Cancer Res. 2009 Jan 1;15(1):361-7. doi: 10.1158/1078-0432.CCR-08-1725.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cornelia L. Trimble, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine 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 20 Jul 2018. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Toxicity (time frame: for the duration of the study, and whenever possible, for an additional 5 years). The study lists 2 primary outcomes in all. 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 NCT00121173, which also lists 1 linked publication.
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 20 Jul 2018.