Vaccine Therapy in Preventing Human Papillomavirus Infection in Younger Cancer Survivors
Sponsor
University of Alabama at Birmingham (Other)
Overall Status
Completed
CT.gov ID
NCT01492582
Collaborator
National Cancer Institute (NCI) (NIH), Merck Sharp & Dohme LLC (Industry)
1,499
5
1
96.6
299.8
3.1
Study Details
Study Description
Brief Summary
This trial will comprehensively evaluate the human papillomavirus (HPV) vaccine in cancer survivors between 9 and 26 years of age by (1) determining the prevalence of HPV vaccine initiation among young cancer survivors, and (2) determining the immune response to and safety/tolerability of the quadrivalent and nonavalent HPV vaccine in young cancer survivors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
Using a cross-sectional survey approach, estimate the prevalence of HPV vaccine non-initiation: a) Examine sociodemographic, behavioral, and medical determinants of HPV vaccine non-initiation.
-
Using a single-arm, phase II, open-label, prospective longitudinal trial design, to evaluate the 3-dose HPV quadrivalent (HPV4) and nonavalent (HPV9) vaccine series and measure the following endpoints: a) Determine immunogenicity following the third and final vaccine dose; b) Identify clinical/host factors influencing immunogenicity; c) Determine the safety/tolerability of the HPV vaccine in cancer survivors.
-
Evaluate the persistence of antibody response at 2 years post vaccine initiation and identify clinical/host factors influencing response persistence.
OUTLINE:
AIM 1 (SURVEY): Patients (ages 18-26 years) or their parents (for patients ages 9-17 years) complete a survey regarding the patient's HPV vaccination status, knowledge of HPV-related disease, and factors important in making decisions regarding vaccination.
AIM 2 (VACCINE EVALUATION): Patients not previously immunized against HPV receive quadrivalent human papillomavirus recombinant vaccine (HPV-6, -11, -16, -18, for patients enrolled on or before 3/1/16) or the nonavalent human papillomavirus recombinant vaccine (HPV-6, -11, -16, -18, -31, -33, -45, -52, -58, for patients enrolled after 3/1/16) intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1499 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Quadrivalent Human Papillomavirus (qHPV) Vaccine in Cancer Survivors: Cross Sectional Survey and Phase II Open-Label Vaccine Trial
Study Start Date
:
Jul 1, 2012
Actual Primary Completion Date
:
Feb 8, 2019
Actual Study Completion Date
:
Jul 20, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Prevention (vaccine therapy) Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) or nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. |
Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine or nonavalent human papillomavirus vaccine (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58)
Given IM
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: survey administration
Ancillary studies
Other: medical chart review
Ancillary studies
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Prevalence of HPV Vaccine Initiation in Cancer Survivors (Aim 1 [Survey]) [At baseline]
The prevalence of HPV vaccine initiation in cancer survivors ages 9 to 26 years
- Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) [1 month following vaccination dose #3]
To demonstrate the non-inferiority of the antibody responses to the HPV vaccine in cancer survivors ages 9 to 26 years when compared to antibody responses of age- and sex-matched historical healthy population.
- Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) [Dose 1 through Month 7]
To demonstrate comparable safety/tolerability of the HPV vaccine in cancer survivors ages 9 to 26 years when compared to age- and sex-matched general population.
Eligibility Criteria
Criteria
Ages Eligible for Study:
9 Years
to 26 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
AIM 1 (SURVEY) (AIM 1 is closed to enrollment)
-
Cancer survivor
-
Between 12 and 60 months after completion of cancer therapy (chemotherapy, radiation, hematopoietic cell transplant [HCT])
-
Scheduled for a return clinic visit at one of the participating institutions
-
English or Spanish-speaking
-
Willing to provide informed consent/assent for study participation
-
AIM 2 (VACCINE EVALUATION)
-
Meets all inclusion criteria outlined in Aim 1
-
Survey response indicated no prior history of HPV vaccination OR patient has no prior history of HPV vaccination by self - or parent/caregiver-report
-
English or Spanish-speaking
-
Medical clearance from treating clinician for study participation
-
Agrees to return to participating institution for 3 HPV vaccine injections
-
Willing to provide informed consent/assent for study participation
Exclusion Criteria:
-
AIM 2 (VACCINE EVALUATION)
-
Allergy to any component of the HPV vaccine including yeast and aluminum
-
Thrombocytopenia (platelet count < 50K) or coagulation disorder that would contraindicate intramuscular injection
-
Transfusion of blood products or intravenous immune globulin within 3 months of study entry
-
Female, and a) currently pregnant or lactating, or b) of childbearing potential and unwilling to avoid pregnancy during the vaccine phase of study (beginning at Day 1 and continuing until at least 4 weeks after all 3 vaccine doses have been administered)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | City of Hope Medical Center | Duarte | California | United States | 91010 |
| 3 | Emory University School Of Medicine | Atlanta | Georgia | United States | 30308 |
| 4 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 5 | Saint Jude Children's Research Hospital | Memphis | Tennessee | United States | 38105 |
Sponsors and Collaborators
- University of Alabama at Birmingham
- National Cancer Institute (NCI)
- Merck Sharp & Dohme LLC
Investigators
- Principal Investigator: Wendy Landier, PhD, CRNP, University of Alabama at Birmingham
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Wendy Landier,
Principal Investigator,
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01492582
Other Study ID Numbers:
- UAB-F141204009/UAB-X141204010
- NCI-2011-03654
- 1R01CA166559
- Merck-IISP#40083
- COH-11034
First Posted:
Dec 15, 2011
Last Update Posted:
Oct 27, 2021
Last Verified:
Oct 1, 2021
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Prevention (Vaccine Therapy) | Survey Arm |
|---|---|---|
| Arm/Group Description | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) or nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. laboratory biomarker analysis: Correlative studies survey administration: Ancillary studies medical chart review: Ancillary studies | Patients (ages 18-26 years) or their parents (for patients ages 9-17 years) complete a survey regarding the patient's HPV vaccination status, knowledge of HPV-related disease, and factors important in making decisions regarding vaccination. |
| Period Title: Overall Study | ||
| STARTED | 453 | 1046 |
| Received First Quadrivalent Vaccine Dose | 254 | 0 |
| Received First Nonavalent Vaccine Dose | 182 | 0 |
| COMPLETED | 384 | 982 |
| NOT COMPLETED | 69 | 64 |
Baseline Characteristics
| Arm/Group Title | Prevention (Vaccine Therapy) | Survey | Total |
|---|---|---|---|
| Arm/Group Description | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) or nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients (ages 18-26 years) or their parents (for patients ages 9-17 years) complete a survey regarding the patient's HPV vaccination status, knowledge of HPV-related disease, and factors important in making decisions regarding vaccination. | Total of all reporting groups |
| Overall Participants | 453 | 1046 | 1499 |
| Age, Customized (Count of Participants) | |||
| 9-15 years |
249
55%
|
508
48.6%
|
757
50.5%
|
| 16-26 years |
204
45%
|
538
51.4%
|
742
49.5%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
195
43%
|
473
45.2%
|
668
44.6%
|
| Male |
258
57%
|
573
54.8%
|
831
55.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
52
11.5%
|
142
13.6%
|
194
12.9%
|
| Not Hispanic or Latino |
400
88.3%
|
900
86%
|
1300
86.7%
|
| Unknown or Not Reported |
1
0.2%
|
4
0.4%
|
5
0.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
0.2%
|
5
0.5%
|
6
0.4%
|
| Asian |
6
1.3%
|
32
3.1%
|
38
2.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
3
0.3%
|
3
0.2%
|
| Black or African American |
96
21.2%
|
170
16.3%
|
266
17.7%
|
| White |
338
74.6%
|
796
76.1%
|
1134
75.7%
|
| More than one race |
10
2.2%
|
24
2.3%
|
34
2.3%
|
| Unknown or Not Reported |
2
0.4%
|
16
1.5%
|
18
1.2%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
453
100%
|
1046
100%
|
1499
100%
|
Outcome Measures
| Title | Prevalence of HPV Vaccine Initiation in Cancer Survivors (Aim 1 [Survey]) |
|---|---|
| Description | The prevalence of HPV vaccine initiation in cancer survivors ages 9 to 26 years |
| Time Frame | At baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who returned an evaluable survey |
| Arm/Group Title | Survey Participants |
|---|---|
| Arm/Group Description | Participants who consented to the survey aim of the study. |
| Measure Participants | 982 |
| Count of Participants [Participants] |
179
39.5%
|
| Title | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) |
|---|---|
| Description | To demonstrate the non-inferiority of the antibody responses to the HPV vaccine in cancer survivors ages 9 to 26 years when compared to antibody responses of age- and sex-matched historical healthy population. |
| Time Frame | 1 month following vaccination dose #3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Quadrivalent Anti-HPV 16, Male, Age 9-15 Years | Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Quadrivalent Anti-HPV 16, Male, Age 16-26 Years | Quadrivalent Anti-HPV 16, Female, Age 16-26 Years | Nonavalent Anti-HPV 16, Male, Age 9-15 Years | Nonavalent Anti-HPV 16, Female, Age 9-15 Years | Nonavalent Anti-HPV 16, Male, Age 16-26 Years | Nonavalent Anti-HPV 16, Female, Age 16-26 Years | Quadrivalent Anti-HPV 18, Male, Age 9-15 Years | Quadrivalent Anti-HPV 18, Female, Age 9-15 Years | Quadrivalent Anti-HPV 18, Male, Age 16-26 Years | Quadrivalent Anti-HPV 18, Female, Age 16-26 Years | Nonavalent Anti-HPV 18, Male, Age 9-15 Years | Nonavalent Anti-HPV 18, Female, Age 9-15 Years | Nonavalent Anti-HPV 18, Male, Age 16-26 Years | Nonavalent Anti-HPV 18, Female, Age 16-26 Years |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. |
| Measure Participants | 65 | 51 | 65 | 28 | 53 | 41 | 32 | 23 | 66 | 54 | 68 | 30 | 50 | 41 | 32 | 28 |
| Geometric Mean (Standard Deviation) [mMu/mL] |
16134.57
(14722.06)
|
15209.73
(15638.30)
|
8740.02
(9625.61)
|
6107.32
(6609.07)
|
16419.64
(14756.37)
|
11763.60
(8082.14)
|
10770.38
(11166.73)
|
11522.87
(10443.38)
|
3472.21
(3769.68)
|
2638.33
(2695.70)
|
1920.01
(2553.81)
|
1009.90
(990.48)
|
5599.80
(4522.19)
|
3457.20
(2510.32)
|
3013.39
(3194.84)
|
3483.29
(6869.27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Survey Participants |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.74 | |
| Confidence Interval |
(1-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Female, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.76 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Male, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 2.15 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Female, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.00 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 18, Male, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.52 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 18, Female, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.48 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 18, Male, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 2.48 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 18, Female, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: QUADRIVALENT Male and female, all age groups: Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26) | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.00 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 16, Male, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Girls 9-15, Boys 9-15, Women 16-26: Petersen LK, Restrepo J, Moreira ED, Jr., et al. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105-115; | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI GMT ratio |
| Estimated Value | 1.23 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 16, Female, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Girls 9-15, Boys 9-15, Women 16-26: Petersen LK, Restrepo J, Moreira ED, Jr., et al. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105-115; | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.12 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 16, Male, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Men 16-26: Castellsague X, Giuliano AR, Goldstone S, et al. Immunogenicity and safety of the 9-valent HPV vaccine in men. Vaccine. 2015;33(48):6892-6901. (HM data). | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.46 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 16, Female, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Girls 9-15, Boys 9-15, Women 16-26: Petersen LK, Restrepo J, Moreira ED, Jr., et al. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105-115; | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.61 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 18, Male, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Girls 9-15, Boys 9-15, Women 16-26: Petersen LK, Restrepo J, Moreira ED, Jr., et al. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105-115; | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.39 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 18, Female, Age 9-15 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Girls 9-15, Boys 9-15, Women 16-26: Petersen LK, Restrepo J, Moreira ED, Jr., et al. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105-115; | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.10 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 18, Male, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Men 16-26: Castellsague X, Giuliano AR, Goldstone S, et al. Immunogenicity and safety of the 9-valent HPV vaccine in men. Vaccine. 2015;33(48):6892-6901. (HM data). | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | 1.65 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Nonavalent Anti-HPV 18, Female, Age 16-26 Years |
|---|---|---|
| Comments | Historical Healthy Population Reference: NONAVALENT Girls 9-15, Boys 9-15, Women 16-26: Petersen LK, Restrepo J, Moreira ED, Jr., et al. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials. Papillomavirus Res. 2017;3:105-115; | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority required that the lower bound of the one-sided 99.688% confidence interval (CI) of the geometric mean titer (GMT) ratio was >0.5. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | lower bound one-sided CI of GMT ratio |
| Estimated Value | -0.44 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | GMT ratio = GMT (cancer survivor) / GMT (historical healthy population) | |
| Title | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) |
|---|---|
| Description | To demonstrate comparable safety/tolerability of the HPV vaccine in cancer survivors ages 9 to 26 years when compared to age- and sex-matched general population. |
| Time Frame | Dose 1 through Month 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Note: 254 participants received the first dose of the quadrivalent vaccine. However, one participant never returned to clinic or returned phone calls after receiving the first vaccine. No follow-up information is available for this participant so only 253 participants are reported in this group. |
| Arm/Group Title | Prevention (Vaccine Therapy)- Quadrivalent | Nonavalent Vaccine |
|---|---|---|
| Arm/Group Description | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. |
| Measure Participants | 253 | 182 |
| Injection site - Pain, any |
90
19.9%
|
84
8%
|
| Injection site - Swelling, any |
15
3.3%
|
15
1.4%
|
| Injection site - Erythema, any |
15
3.3%
|
17
1.6%
|
| Systemic - Headache |
51
11.3%
|
33
3.2%
|
| Systemic - Fever |
17
3.8%
|
15
1.4%
|
| Systemic - Nausea |
29
6.4%
|
41
3.9%
|
| Systemic - Dizziness |
5
1.1%
|
2
0.2%
|
| Systemic - Fatigue |
47
10.4%
|
24
2.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Survey Participants |
|---|---|---|
| Comments | Injection site - Pain, any; Injection site - Swelling, any; Injection site - Erythema, any; Systemic - Nausea Historical Healthy Population: Reported from Gardasil Package Insert 04/2015, Tables 1, 2, 5, and 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared, Corrected | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Survey Participants |
|---|---|---|
| Comments | Systemic - Fever Historical Healthy Population: Reported from Gardasil Package Insert 04/2015, Tables 1, 2, 5, and 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03 |
| Comments | ||
| Method | Chi-squared, Corrected | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Survey Participants |
|---|---|---|
| Comments | Systemic - Dizziness Historical Healthy Population: Reported from Gardasil Package Insert 04/2015, Tables 1, 2, 5, and 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.48 |
| Comments | ||
| Method | Chi-squared, Corrected | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Female, Age 9-15 Years |
|---|---|---|
| Comments | Injection site - Pain, any; Injection site - Swelling, any; Injection site - Erythema, any; Systemic - Nausea; Systemic - Fatigue Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared, Corrected | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Female, Age 9-15 Years |
|---|---|---|
| Comments | Systemic - Headache Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.07 |
| Comments | ||
| Method | Chi-squared, Corrected | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Female, Age 9-15 Years |
|---|---|---|
| Comments | Systemic - Fever Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.28 |
| Comments | ||
| Method | Chi-squared, Corrected | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Quadrivalent Anti-HPV 16, Female, Age 9-15 Years |
|---|---|---|
| Comments | Systemic - Dizziness Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.45 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Adverse Events
| Time Frame | Other (Not Including Serious) Adverse Events: Nonavalent: 7 days after each vaccine dose Quadrivalent: 14 days after each vaccine dose Serious Adverse Events were reported up to Month 7 (no SAEs occurred within 7-14 days of each vaccine dose). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | No adverse events are reported for the survey arm participants as adverse events were not monitored/assessed for participants in this arm. Note: 254 participants received the first dose of the quadrivalent vaccine. However, one participant never returned to clinic or returned phone calls after receiving the first vaccine. No follow-up information is available for this participant so only 253 participants are reported in this group. | |||
| Arm/Group Title | Prevention (Vaccine Therapy)- Quadrivalent | Prevention (Vaccine Therapy)- Nonavalent Vaccine | ||
| Arm/Group Description | Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18, for patients enrolled on or before 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | Patients receive nonavalent human papillomavirus (types 6, 11, 16, 18, 31, 33, 45, 52, and 58, for patients enrolled after 3/1/16) recombinant vaccine intramuscularly on day 1, at 8-12 weeks, and at 24-32 weeks. | ||
All Cause Mortality |
||||
| Prevention (Vaccine Therapy)- Quadrivalent | Prevention (Vaccine Therapy)- Nonavalent Vaccine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/253 (0%) | 0/182 (0%) | ||
Serious Adverse Events |
||||
| Prevention (Vaccine Therapy)- Quadrivalent | Prevention (Vaccine Therapy)- Nonavalent Vaccine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/253 (4.3%) | 7/182 (3.8%) | ||
| Endocrine disorders | ||||
| Hospitalization for endocrine disorder | 2/253 (0.8%) | 0/182 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hospitalization for fluid-electrolyte disorder | 0/253 (0%) | 1/182 (0.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Hospitalization for musculoskeletal issue | 4/253 (1.6%) | 0/182 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Relapse of primary cancer | 3/253 (1.2%) | 1/182 (0.5%) | ||
| Subsequent malignant neoplasm | 0/253 (0%) | 1/182 (0.5%) | ||
| Nervous system disorders | ||||
| Hospitalization for neurologic disorder | 0/253 (0%) | 1/182 (0.5%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Pregnancy | 2/253 (0.8%) | 1/182 (0.5%) | ||
| Psychiatric disorders | ||||
| Hospitalization for psychiatric disorder | 0/253 (0%) | 1/182 (0.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Erythema nodosum | 0/253 (0%) | 1/182 (0.5%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Prevention (Vaccine Therapy)- Quadrivalent | Prevention (Vaccine Therapy)- Nonavalent Vaccine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 129/253 (51%) | 108/182 (59.3%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 29/253 (11.5%) | 41/182 (22.5%) | ||
| General disorders | ||||
| Injection Site Pain or Tenderness, any | 90/253 (35.6%) | 84/182 (46.2%) | ||
| Injection Site Swelling, any | 15/253 (5.9%) | 15/182 (8.2%) | ||
| Injection Site Erythema, any | 15/253 (5.9%) | 17/182 (9.3%) | ||
| Headache | 51/253 (20.2%) | 33/182 (18.1%) | ||
| Fever (≥100.0⁰F) | 17/253 (6.7%) | 15/182 (8.2%) | ||
| Fatigue | 47/253 (18.6%) | 24/182 (13.2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE 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 | Dr. Wendy Landier, Deputy Director, Institute for Cancer Outcomes and Survivorship |
|---|---|
| Organization | University of Alabama at Birmingham |
| Phone | (205) 638-2120 |
| wlandier@peds.uab.edu |
Responsible Party:
Wendy Landier,
Principal Investigator,
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01492582
Other Study ID Numbers:
- UAB-F141204009/UAB-X141204010
- NCI-2011-03654
- 1R01CA166559
- Merck-IISP#40083
- COH-11034
First Posted:
Dec 15, 2011
Last Update Posted:
Oct 27, 2021
Last Verified:
Oct 1, 2021