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Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3)

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ClinicalTrials.gov Identifier: NCT00988559
Recruitment Status : Completed
First Posted : October 2, 2009
Results First Posted : July 9, 2018
Last Update Posted : July 9, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HPV16 Positive
Cervical Intraepithelial Neoplasia (CIN 2/3)
Interventions Biological: DNA vaccination
Device: Gene gun vaccine
Biological: intramuscular vaccination
Biological: intra-lesional vaccine administration
Procedure: therapeutic resection of the lesion
Drug: imiquimod
Enrollment 132
Recruitment Details  
Pre-assignment Details

132 subjects signed consents to be screened for eligibility

  • 93 subjects signed consents, but did not meet the eligibility criteria to start the study (screen failures)
  • 39 subjects were assigned to a treatment group in the study
Arm/Group Title PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Hide Arm/Group Description

Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

Gene gun vaccine: 8 micrograms (group 1) or 16 micrograms (group 2)

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intramuscular vaccination: 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

imiquimod: imiquimod applied to the cervix by the physician

Period Title: Overall Study
Started 10 11 11 7
Completed 9 9 9 6
Not Completed 1 2 2 1
Reason Not Completed
Withdrawal by Subject             1             1             0             1
Pregnancy             0             1             1             0
Lost to Follow-up             0             0             1             0
Arm/Group Title PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7 Total
Hide Arm/Group Description

Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

Gene gun vaccine: 8 micrograms (group 1) or 16 micrograms (group 2)

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intramuscular vaccination: 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

imiquimod: imiquimod applied to the cervix by the physician

Total of all reporting groups
Overall Number of Baseline Participants 10 11 11 7 39
Hide Baseline Analysis Population Description
Participants enrolled in the study who received at least one study intervention
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants 11 participants 11 participants 7 participants 39 participants
25.5
(20 to 44)
26
(21 to 35)
26
(23 to 35)
26.14
(24 to 29)
25.91
(20 to 44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 11 participants 7 participants 39 participants
Female
10
 100.0%
11
 100.0%
11
 100.0%
7
 100.0%
39
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 11 participants 7 participants 39 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  10.0%
1
   9.1%
0
   0.0%
0
   0.0%
2
   5.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
5
  45.5%
2
  18.2%
4
  57.1%
11
  28.2%
White
9
  90.0%
5
  45.5%
9
  81.8%
3
  42.9%
26
  66.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Related Serious Adverse Events
Hide Description Presence of intervention-related serious adverse events as defined by CTCAE
Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Related Serious Adverse Events
Arm/Group Title PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Hide Arm/Group Description:

Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

Gene gun vaccine: 8 micrograms (group 1) or 16 micrograms (group 2)

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intramuscular vaccination: 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

imiquimod: imiquimod applied to the cervix by the physician

Overall Number of Participants Analyzed 10 11 11 7
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title Absence of CIN2/3 Lesion by Week 15
Hide Description Number of participants with no CIN2/3 lesion at the week 15 visit
Time Frame 15 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of participants who had no CIN2/3 at the week 15 resection
Arm/Group Title PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Hide Arm/Group Description:

Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

Gene gun vaccine: 8 micrograms (group 1) or 16 micrograms (group 2)

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intramuscular vaccination: 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

imiquimod: imiquimod applied to the cervix by the physician

Overall Number of Participants Analyzed 9 9 9 6
Measure Type: Count of Participants
Unit of Measure: Participants
2
  22.2%
3
  33.3%
3
  33.3%
1
  16.7%
Time Frame 41 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Hide Arm/Group Description

Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

Gene gun vaccine: 8 micrograms (group 1) or 16 micrograms (group 2)

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intramuscular vaccination: 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

DNA vaccination: vaccination with pNGVL4a-CRT/E7(detox)

intra-lesional vaccine administration: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally

therapeutic resection of the lesion: at week 15, all residual lesions will be resected

imiquimod: imiquimod applied to the cervix by the physician

All-Cause Mortality
PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/11 (0.00%)      0/11 (0.00%)      0/7 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
PMED Delivery - Groups 1 and 2 IM Injections - Groups 5 and 6 Intralesional Delivery - Group 3 and 4 Intralesional Delivery + Imiquimod - Group 7
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      11/11 (100.00%)      10/11 (90.91%)      7/7 (100.00%)    
General disorders         
Injection site reactions  [1]  8/10 (80.00%)  43 6/11 (54.55%)  10 1/11 (9.09%)  1 0/7 (0.00%)  0
General pain, fever, malaise/fatigue  [2]  8/10 (80.00%)  44 8/11 (72.73%)  38 8/11 (72.73%)  41 7/7 (100.00%)  37
Infections and infestations         
Rash   0/10 (0.00%)  0 2/11 (18.18%)  2 0/11 (0.00%)  0 1/7 (14.29%)  1
Nervous system disorders         
Limb numbness   1/10 (10.00%)  5 1/11 (9.09%)  1 0/11 (0.00%)  0 0/7 (0.00%)  0
Psychiatric disorders         
Depression   1/10 (10.00%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0 1/7 (14.29%)  1
Reproductive system and breast disorders         
Vaginal bleeding/spotting  [3]  0/10 (0.00%)  0 0/11 (0.00%)  0 3/11 (27.27%)  3 1/7 (14.29%)  6
Respiratory, thoracic and mediastinal disorders         
Laryngeal inflammation   0/10 (0.00%)  0 1/11 (9.09%)  2 0/11 (0.00%)  0 1/7 (14.29%)  1
Indicates events were collected by systematic assessment
[1]
Local injection site reactions
[2]
Abdominal discomfort, cramping, fatigue, flu like symptoms, headaches, muscle/joint aches, nausea, pain, pruritus
[3]
vaginal bleeding or spotting
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Cornelia L. Trimble, MD
Organization: Johns Hopkins University
Phone: 410-502-0512
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00988559     History of Changes
Other Study ID Numbers: J0866
P50CA098252 ( U.S. NIH Grant/Contract )
1R21CA128232 ( U.S. NIH Grant/Contract )
NA_00020850 ( Other Identifier: JHM IRB )
First Submitted: October 1, 2009
First Posted: October 2, 2009
Results First Submitted: October 27, 2016
Results First Posted: July 9, 2018
Last Update Posted: July 9, 2018