HPV Positive Oropharyngeal Squamous Cell Carcinoma, HPV-Related Carcinoma, Oropharynx Cancer
Conditions
Brief summary
Combination immune checkpoint inhibitor and DNA vaccine will result in clearance of HPV DNA biomarkers (oral and/or plasma) for patients with persistent HPV-16 E6/E7 DNA (HPV biomarker) after treatment with curative intent.
Detailed description
Objectives: Primary Objectives: To determine whether combination immune checkpoint inhibitor, alone or together with a DNA vaccine will result in clearance of HPV biomarkers for patients at risk of disease progression. Secondary Objective(s): 1. To evaluate the time to progression among patients with detectable HPV DNA when treated with the durvalumab/MEDI0457 versus durvalumab monotherapy versus observation. 2. To assess the toxicity of durvalumab and MEDI0457 in the adjuvant setting. Exploratory Objective(s): 1. To determine whether anti-PD-L1 alone or together with an HPV DNA vaccine will enhance HPV E6/E7-specific and/or mutation-associated neoantigen (MANA)-specific T cell responses and whether these responses correlate with enhanced clearance of HPV as measured by DNA in oral rinses and/or plasma. 2. To determine whether anti-PD-L1 alone or together with an HPV DNA vaccine will enhance HPV 16 E6/E7-specific IgG and whether these responses correlate with enhanced clearance of HPV as measured by DNA in oral rinses and/or plasma
Interventions
DRUGMEDI0457
MEDI0457 is an investigational drug that will be administered with the Cellectra Device in this study
DRUGDurvalumab
Durvalumab is an investigational drug in this study.
Sponsors
AstraZeneca
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. * Men and women \>or = 18 years at the time of study entry. * Histologically or cytologically proven HPV16-positive or p16-positive oropharyngeal squamous cell carcinoma. * Eastern Cooperative Oncology Group (ECOG) 0-1 (Appendix A) * Completion of primary therapy curative intent )surgery based or radiation based) within the past year (date of last treatment + 1 year) OR newly diagnosed with a plan for treatment with curative intent OR currently in primary treatment with curative intent. * Body weight or = 30kg * Adequate organ function as follows: * Absolute neutrophil count (ANC) \> or = 1000/mm3 * Platelet count \> or = 75 x 109/L(\> or = 75,000 per mm3) * Hemoglobin \> or =9 g/dL * Creatinine \< or = 1.5 x institutional ULN or creatinine clearance (CrCI) \> or = 40mL/min (if using Cockcroft-Gault formula below): Female CrCI = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCI= (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL * Total Bilirubin \< or = 1.5 x institutional ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) * AST(SGOT)/ALT(SGPT) \< or = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be \< or = 5x ULN * Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 217 days after the last dose of durvalumab. * The effects of Durvalumab and MEDI0475 on the developing human fetus are unknown. Women of child-bearing potential (WOCBP) and mes must agree to use at least one highly effective method of contraception (hormonal or barrier method form of birth control; abstinence) prior to study entry and for the duration of study participation and for up to 217 days after the last dose of Durvalumab or MEDI0457. * Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she must inform her treating physician immediately. * WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of screening. * Women must not be breastfeeding * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women \> or =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). * Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. * Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC guidelines must be obtained before the performance of any protocol related procedures that are not part of normal care. * Subjects must be competent to report AEs, understand the drug dosing schedule and use of medications to control AEs. * Individuals of all races and ethnic groups are eligible for this trial. There is no bias towards age, gender or race in the clinical trial outlined. This trial is open to accrual of men and women who meet the inclusion/
Exclusion criteria
outlined.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants in whom there is clearance of Human Papiloma Virus (HPV) biomarkers post-intervention | Up to 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | Up to 5 years | Time until progression, followed for up to five years, among patients with detectable HPV DNA when treated with the durvalumab/MEDI0457 versus durvalumab monotherapy versus observation. |
| Safety of Study Drugs | Up to 30 days after the last dose of study drug | Adverse events will be reviewed to determine the safety of durvalumab and MEDI0457 in the adjuvant setting. Observed Adverse events and toxicities will be tabulated by treatment group, type and grade. AEs and other toxicities will be graded using NCI Common Terminology Criteria for Adverse Events 5.0 (CTCAE). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clearance of HPV Measured by DNA in participants with HPV E6/E7-specific and MANA-specific T-cell response | Up to 5 years | Clearance of HPV as measured by DNA in oral rinses and/or plasma (milliliters) in participants with HPV E6/E7-specific and mutation-associated neoantigen (MANA)-specific T-cell responses. |
| Clearance of HPV Measured by DNA in participants with HPV E6/E7-specific IgG | Up to 5 years | Clearance of HPV as measured by DNA in oral rinses and/or plasma (milliliters) in participants with HPV E6/E7-specific IgG |
Countries
United States
Outcome results
None listed