Cervical Cancer, Precancerous Condition
Conditions
Keywords
cervical cancer, cervical intraepithelial neoplasia grade 2, cervical intraepithelial neoplasia grade 3
Brief 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. 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.
Interventions
BIOLOGICALpNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine
recombinant DNA vaccine
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed cervical intraepithelial neoplasia (CIN2/3) * Human papillomavirus-16-positive disease PATIENT CHARACTERISTICS: \- Age: \> 18 Other * Not pregnant * Immunocompetent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Toxicity | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Regression of CIN3 Lesions | 15 weeks | Number of participants with absence of CIN3 lesions at week 15 |
| Number of Participants With T-cell Immune Responses in the Blood | 41 weeks | Systemic T-cell response as measured by γ-INF enzyme-linked immunospot assays (ELISpot) |
| Number of Participants With Correlated Measures of Immune Response With Clinical Response | 9 months | Number of participants whose t-cell immune responses correlated with histologic regression of disease or viral clearance of HPV |
| Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model | 9 months | Number of participants whose T-cell immune responses correlated with the immune responses observed in the preclinical model |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose 3-500mcg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM
pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine | 3 |
| Intermediate Dose 3-1mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM
pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine | 3 |
| High Dose 3-3mg doses of pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine administered IM
pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine | 9 |
| Total | 15 |
Baseline characteristics
| Characteristic | Low Dose | Intermediate Dose | High Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 9 Participants | 14 Participants |
| Age, Continuous | 26 years | 29 years | 30.3 years | 28.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 9 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 7 Participants | 9 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 9 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 5 / 9 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 9 |
Outcome results
Primary
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.
Time frame: for the duration of the study, and whenever possible, for an additional 5 years
Population: per protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose | Efficacy | 0 Participants |
| Intermediate Dose | Efficacy | 0 Participants |
| High Dose | Efficacy | 3 Participants |
Primary
Safety and Toxicity
Number of participants with serious adverse events (SAE) according to CTCAE 3.0 grading.
Time frame: for the duration of the study, and whenever possible, for an additional 5 years
Population: per protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose | Safety and Toxicity | 0 Participants |
| Intermediate Dose | Safety and Toxicity | 0 Participants |
| High Dose | Safety and Toxicity | 0 Participants |
Secondary
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
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose | Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model | 0 Participants |
| Intermediate Dose | Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model | 0 Participants |
| High Dose | Number of Participants With Correlated Measures of Immune Responses With the Preclinical Model | 0 Participants |
Secondary
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
Time frame: 9 months
Population: All participants who received all 3 vaccinations
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose | Number of Participants With Correlated Measures of Immune Response With Clinical Response | 0 Participants |
| Intermediate Dose | Number of Participants With Correlated Measures of Immune Response With Clinical Response | 0 Participants |
| High Dose | Number of Participants With Correlated Measures of Immune Response With Clinical Response | 0 Participants |
Secondary
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)
Time frame: 41 weeks
Population: all patients who completed all 3 vaccinations
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose | Number of Participants With T-cell Immune Responses in the Blood | 0 Participants |
| Intermediate Dose | Number of Participants With T-cell Immune Responses in the Blood | 0 Participants |
| High Dose | Number of Participants With T-cell Immune Responses in the Blood | 0 Participants |
Secondary
Regression of CIN3 Lesions
Number of participants with absence of CIN3 lesions at week 15
Time frame: 15 weeks
Population: per protocol; participants who had no CIN3 lesions assessed by colposcopy and biopsy(ies) at the week 15 visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose | Regression of CIN3 Lesions | 0 Participants |
| Intermediate Dose | Regression of CIN3 Lesions | 0 Participants |
| High Dose | Regression of CIN3 Lesions | 3 Participants |