Cancer Survivor, Prevention of Human Papillomavirus Infection
Conditions
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.
Detailed description
PRIMARY OBJECTIVES: I. 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. II. 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. III. 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.
Interventions
BIOLOGICALquadrivalent 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
OTHERlaboratory biomarker analysis
Correlative studies
OTHERsurvey administration
Ancillary studies
OTHERmedical chart review
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Merck Sharp & Dohme LLC
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 26 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 453 |
| 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. | 1,046 |
| Total | 1,499 |
Baseline characteristics
| Characteristic | Prevention (Vaccine Therapy) | Survey | Total |
|---|---|---|---|
| Age, Customized 16-26 years | 204 Participants | 538 Participants | 742 Participants |
| Age, Customized 9-15 years | 249 Participants | 508 Participants | 757 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 142 Participants | 194 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 400 Participants | 900 Participants | 1300 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 32 Participants | 38 Participants |
| Race (NIH/OMB) Black or African American | 96 Participants | 170 Participants | 266 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 24 Participants | 34 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 16 Participants | 18 Participants |
| Race (NIH/OMB) White | 338 Participants | 796 Participants | 1134 Participants |
| Region of Enrollment United States | 453 participants | 1046 participants | 1499 participants |
| Sex: Female, Male Female | 195 Participants | 473 Participants | 668 Participants |
| Sex: Female, Male Male | 258 Participants | 573 Participants | 831 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 253 | 0 / 182 |
| other Total, other adverse events | 129 / 253 | 108 / 182 |
| serious Total, serious adverse events | 11 / 253 | 7 / 182 |
Outcome results
Primary
Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation])
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Survey Participants | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 16134.57 mMu/mL | Standard Deviation 14722.06 |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 15209.73 mMu/mL | Standard Deviation 15638.3 |
| Quadrivalent Anti-HPV 16, Male, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 8740.02 mMu/mL | Standard Deviation 9625.61 |
| Quadrivalent Anti-HPV 16, Female, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 6107.32 mMu/mL | Standard Deviation 6609.07 |
| Nonavalent Anti-HPV 16, Male, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 16419.64 mMu/mL | Standard Deviation 14756.37 |
| Nonavalent Anti-HPV 16, Female, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 11763.60 mMu/mL | Standard Deviation 8082.14 |
| Nonavalent Anti-HPV 16, Male, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 10770.38 mMu/mL | Standard Deviation 11166.73 |
| Nonavalent Anti-HPV 16, Female, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 11522.87 mMu/mL | Standard Deviation 10443.38 |
| Quadrivalent Anti-HPV 18, Male, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 3472.21 mMu/mL | Standard Deviation 3769.68 |
| Quadrivalent Anti-HPV 18, Female, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 2638.33 mMu/mL | Standard Deviation 2695.7 |
| Quadrivalent Anti-HPV 18, Male, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 1920.01 mMu/mL | Standard Deviation 2553.81 |
| Quadrivalent Anti-HPV 18, Female, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 1009.90 mMu/mL | Standard Deviation 990.48 |
| Nonavalent Anti-HPV 18, Male, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 5599.80 mMu/mL | Standard Deviation 4522.19 |
| Nonavalent Anti-HPV 18, Female, Age 9-15 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 3457.20 mMu/mL | Standard Deviation 2510.32 |
| Nonavalent Anti-HPV 18, Male, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 3013.39 mMu/mL | Standard Deviation 3194.84 |
| Nonavalent Anti-HPV 18, Female, Age 16-26 Years | Immunogenicity of the HPV Vaccine in Cancer Survivors (Anti-HPV 16 and 18 Geometric Mean Titers) (Aim 2 [Vaccine Evaluation]) | 3483.29 mMu/mL | Standard Deviation 6869.27 |
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: Historical Healthy Population Reference:~QUADRIVALENT~Male and female, all age groups:~Merck Pub 9883616 (Gardasil Package Insert, April 2011, pp 24-26)
Comparison: 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;
Comparison: 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;
Comparison: 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).
Comparison: 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;
Comparison: 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;
Comparison: 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;
Comparison: 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).
Comparison: 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;
Primary
Prevalence of HPV Vaccine Initiation in Cancer Survivors (Aim 1 [Survey])
The prevalence of HPV vaccine initiation in cancer survivors ages 9 to 26 years
Time frame: At baseline
Population: Participants who returned an evaluable survey
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Survey Participants | Prevalence of HPV Vaccine Initiation in Cancer Survivors (Aim 1 [Survey]) | 179 Participants |
Primary
Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation])
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Injection site - Pain, any | 90 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Injection site - Swelling, any | 15 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Injection site - Erythema, any | 15 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Headache | 51 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Fever | 17 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Nausea | 29 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Dizziness | 5 participants |
| Survey Participants | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Fatigue | 47 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Fatigue | 24 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Injection site - Pain, any | 84 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Fever | 15 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Injection site - Swelling, any | 15 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Dizziness | 2 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Injection site - Erythema, any | 17 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Nausea | 41 participants |
| Quadrivalent Anti-HPV 16, Female, Age 9-15 Years | Safety/Tolerability of the HPV Vaccine in Cancer Survivors (Aim 2 [Vaccine Evaluation]) | Systemic - Headache | 33 participants |
Comparison: 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 6p-value: <0.001Chi-squared, Corrected
Comparison: Systemic - Fever Historical Healthy Population: Reported from Gardasil Package Insert 04/2015, Tables 1, 2, 5, and 6p-value: 0.03Chi-squared, Corrected
Comparison: Systemic - Dizziness Historical Healthy Population: Reported from Gardasil Package Insert 04/2015, Tables 1, 2, 5, and 6p-value: 0.48Chi-squared, Corrected
Comparison: 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 5p-value: <0.001Chi-squared, Corrected
Comparison: Systemic - Headache Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5p-value: 0.07Chi-squared, Corrected
Comparison: Systemic - Fever Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5p-value: 0.28Chi-squared, Corrected
Comparison: Systemic - Dizziness Historical Healthy Population - As reported by Moreira et. al, 2016, Pediatrics, Table 5p-value: 0.45Fisher Exact