Human Papillomavirus Infection, Stage III Oral Cavity Squamous Cell Carcinoma, Stage III Oropharyngeal Squamous Cell Carcinoma, Stage II Oral Cavity Squamous Cell Carcinoma, Stage II Oropharyngeal Squamous Cell Carcinoma, Stage I Oral Cavity Squamous Cell Carcinoma, Stage I Oropharyngeal Squamous Cell Carcinoma, Stage IVA Oral Cavity Squamous Cell Carcinoma, Stage IVA Oropharyngeal Squamous Cell Carcinoma, Stage IVB Oral Cavity Squamous Cell Carcinoma, Stage IVB Oropharyngeal Squamous Cell Carcinoma, Stage IVC Oropharyngeal Squamous Cell Carcinoma
Conditions
Brief summary
This pilot clinical trial studies how well durvalumab before surgery works in treating patients with oral cavity or oropharynx cancer. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES: I. To investigate the effect of durvalumab on local and systemic immune activation by HPV status in patients with oral cavity and oropharynx head and neck squamous cell carcinoma (HNSCC). II. To examine the effects of durvalumab on systemic immune response to HPV and tumor associated antigens. III. To examine the effects of durvalumab on immune regulatory mechanisms. IV. To explore the association between levels of immune-regulatory micro-ribonucleic acid (miR) in plasma and saliva and immune response. SECONDARY OBJECTIVES: I. Investigate the effect of the treatment with durvalumab on the computed tomography (CT) scan and positron emission tomography (PET) scan response. II. Evaluate the safety of a short induction treatment with durvalumab. OUTLINE: Patients receive durvalumab intravenously (IV) over approximately 60 minutes on day 1. Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab, patients undergo surgery. Patients may receive an additional dose of durvalumab if time to surgery is longer than 30 days. After completion of study treatment, patients are followed up for 90 days.
Interventions
BIOLOGICALDurvalumab
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed HNSCC of the oral cavity (OC; more than 90% patients have HPV negative cancer) or oropharynx (about 60-80% of patient have HPV positive cancer) * Presence of radiologically of clinically documented disease. All radiology studies must be performed within 28 days prior to registration * Any stage, considered candidates for surgery and planned for surgery either by robotic or by standard surgical technique * Documentation of HPV tested by polymerase chain reaction (PCR) (resulted or pending) * Willing to provide consent for an additional tissue biopsy for research purposes, to allow a part of their surgical tumor tissue to be utilized for research (in case tumor tissue has not already been saved in the tumor tissue bank), and to donate samples of blood and saliva collected weekly through the treatment * All patients must have provided informed consent for correlative studies * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Patients must have no prior exposure to immune-mediated therapy, including anti- cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1, anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines * At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as \> or = 10 mm in the longest diameter (except lymph nodes, which must have a short axis \> or = 15 mm) with CT or magnetic resonance imaging (MRI) or clinical measurement and that is suitable for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines * Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelet count \>= 100 x 10\^9/L * Hemoglobin \>= 9.0 g/dL * Serum bilirubin =\< 1.5 x upper limit of normal (ULN) (institutional upper limit of normal) * Total bilirubin is less than or equal to ULN, except the case in which the elevated total bilirubin is not a sign of liver disease, such as the Gilbert Syndrome, in which case a Total Bilirubin less than or equal to 2X ULN is acceptable. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN * Serum creatinine clearance (CL) \> 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance * Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: \>= 60 years old and no menses for \>= 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry * In accordance with National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) policy, protocol treatment is to begin within 2 working days of patient registration * Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act \[HIPAA\] in the United States of American \[USA\], European Union \[EU\] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations * Age 18 years or older at time of study entry. * Subject 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
Exclusion criteria
* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study * Participation in another clinical study with an investigational product during the last 6 months (mo) * Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab * Receipt of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within the last 6 mo (before the first dose of Durvalumab). * Mean QT interval corrected for heart rate (corrected QT \[QTc\]) \>= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correction * Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid * Any unresolved toxicity (\> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2) from previous anti-cancer therapy; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy) * Any prior grade \>= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> grade 1 * Active or prior documented autoimmune disease within the past 2 years; NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded * Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) * History of primary immunodeficiency * History of allogeneic organ transplant * History of hypersensitivity to durvalumab or any excipient * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent * Known history of previous clinical diagnosis of tuberculosis * Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab * Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control * Patients with body weight \<= 30 kg * Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Immune Response to Tumor Associated Antigens Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | Up to 18 months | Lab results will be compared between patients who are HPV+ and HPV- using 2 sample t-tests. These measures will be compared in several ways. First, baseline, pre-treatment levels will be examined using descriptive statistics (n, mean, standard deviations, range). These measures will be examined overall and by HPV (+/-) groups. For each measure, and time point, 95% confidence intervals will be estimated. Next, two sample t-tests will be performed to compare levels of the measures at baseline. Next, measures taken post-treatment will be examined in a similar manner (descriptive statistics and 2- |
| Regulatory Responses Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry | Up to 18 months | Concentration of certain regulatory cells will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Tes |
| Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | Baseline and one week post treatment start | Percent change of levels of immune-regulatory miRs assessed in saliva assessed pre-treatment and one week post-treatment. |
| Immune-regulatory miR Responses as Measured in Tumor Tissue Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | Up to 18 months | Levels of immune-regulatory miRs assessed in blood, saliva and tumor tissue will be assessed pre- and post- treatments. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. In addition, correlations between the different methods will be examined (i.e., correlation between saliva and blood measures, saliva and tumor measures, and blood and tumor measures). |
| Immune Effector Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry | Up to 18 months | Concentration of certain immune effector will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Test |
| Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | At baseline and at one week post treatment start | Percent change of levels of immune-regulatory miRs assessed in plasma assessed pre-treatment and one week post-treatment. |
| Systemic Immune Response to HPV Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | Up to 18 months | Lab results will be compared between patients who are HPV+ and HPV- using 2 sample t-tests. These measures will be compared in several ways. First, baseline, pre-treatment levels will be examined using descriptive statistics (n, mean, standard deviations, range). These measures will be examined overall and by HPV (+/-) groups. For each measure, and time point, 95% confidence intervals will be estimated. Next, two sample t-tests will be performed to compare levels of the measures at baseline. Next, measures taken post-treatment will be examined in a similar manner (descriptive statistics and 2- |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Standardized Uptake Value (SUV) as Measured by PET Scans | Up to 18 months | Change in SUV activity as measured by PET scans from baseline to post-treatment not specific to HPV status. |
| Tumor Diameter Assessed Using RECIST Version 1.1 Criteria | Up to 18 months | Change in tumor diameters will be compared between groups (HPV +/-) pre- and post- treatment. |
| Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | At baseline (pre-treatment), during scheduled treatment and up to the 90-day follow up period after the last dose of study drug administered, with a median of 1 month and maximum of 13 months | AEs will be coded using the Medical Dictionary for Regulatory Activities to their organ class by preferred term. Coded AEs will be displayed by frequency, severity, and relationship to treatment (durvalumab) in the safety population. In addition, summary tables will be generated for the following situations: 1) fatigue, diarrhea, nausea and skin rash; 2) Immune-mediated reactions of any grade; 3) other adverse events graded as 3 or more by CTCAE Version 4.03; 4) Durvalumab dose reductions; 5) discontinuations of treatment with durvalumab, with specification of reason for discontinuation; and 6) changes in the surgical treatment schedule. Toxicity grades Grade I (mild), Grade II (moderate), Grade III (severe), Grade IV (life threatening) and Grade V (fatal). Toxicities of greater than or equal to Grade III (except infusion reaction) are considered worse outcomes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Durvalumab, Surgery) - HPV Negative Patients receive durvalumab IV over approximately 60 minutes on day 1. Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab, patients undergo surgery. Patients may receive an additional dose of durvalumab if time to surgery is longer than 30 days.
Durvalumab: Given IV
Therapeutic Conventional Surgery: Undergo surgery
HPV negative | 11 |
| Treatment (Durvalumab, Surgery) - HPV Positive Patients receive durvalumab IV over approximately 60 minutes on day 1. Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab, patients undergo surgery. Patients may receive an additional dose of durvalumab if time to surgery is longer than 30 days.
Durvalumab: Given IV
Therapeutic Conventional Surgery: Undergo surgery
HPV positive | 6 |
| Total | 17 |
Baseline characteristics
| Characteristic | Treatment (Durvalumab, Surgery) - HPV Negative | Treatment (Durvalumab, Surgery) - HPV Positive | Total |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 9.2 | 58.0 years STANDARD_DEVIATION 6.5 | 58.3 years STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 5 Participants | 16 Participants |
| Region of Enrollment United States | 11 participants | 6 participants | 17 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 11 | 0 / 6 |
| other Total, other adverse events | 11 / 11 | 6 / 6 |
| serious Total, serious adverse events | 5 / 11 | 0 / 6 |
Outcome results
Primary
Immune Effector Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry
Concentration of certain immune effector will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Test
Time frame: Up to 18 months
Population: This pre-specified outcome is dependent upon 1) patients having a measurable response and 2) availability of comparable cohorts of HPV positive and negative samples. Since there was a lack of measurable clinical response in all patients and the enrolled cohorts were unbalanced, the data for this outcome was not measured/evaluated and therefore is not available for analysis.
Primary
Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR)
Percent change of levels of immune-regulatory miRs assessed in plasma assessed pre-treatment and one week post-treatment.
Time frame: At baseline and at one week post treatment start
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 181 | 25.7 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 223 | 13.7 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 155 | 19.7 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 335 | 12.5 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 20a | -15.6 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 125 | 43.4 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 146 | 27.5 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 125 | 194.5 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 146 | 1251.6 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 155 | 814 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 181 | 893.2 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 20a | 520.6 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 223 | 1031.2 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 335 | 1166.0 percent change from baseline |
Primary
Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR)
Percent change of levels of immune-regulatory miRs assessed in saliva assessed pre-treatment and one week post-treatment.
Time frame: Baseline and one week post treatment start
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 181 | 114.4 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 223 | 66.4 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 155 | 141.2 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 335 | 249.4 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 20a | 163.9 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 125 | 351.6 percent change from baseline |
| Treatment (Durvalumab, Surgery) | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 146 | 251.3 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 125 | 64.9 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 146 | 105.3 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 155 | 255.0 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 181 | 232.5 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 20a | 113.1 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 223 | 199.2 percent change from baseline |
| Treatment (Durvalumab, Surgery) - HPV Positive | Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR) | miR 335 | 150.2 percent change from baseline |
Primary
Immune-regulatory miR Responses as Measured in Tumor Tissue Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR)
Levels of immune-regulatory miRs assessed in blood, saliva and tumor tissue will be assessed pre- and post- treatments. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. In addition, correlations between the different methods will be examined (i.e., correlation between saliva and blood measures, saliva and tumor measures, and blood and tumor measures).
Time frame: Up to 18 months
Population: This pre-specified outcome is dependent upon 1) patients having a measurable response and 2) availability of comparable cohorts of HPV positive and negative samples. Since there was a lack of measurable clinical response in all patients and the enrolled cohorts were unbalanced, the data for this outcome was not measured/evaluated and therefore is not available for analysis.
Primary
Regulatory Responses Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry
Concentration of certain regulatory cells will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Tes
Time frame: Up to 18 months
Population: This pre-specified outcome is dependent upon 1) patients having a measurable response and 2) availability of comparable cohorts of HPV positive and negative samples. Since there was a lack of measurable clinical response in all patients and the enrolled cohorts were unbalanced, the data for this outcome was not measured/evaluated and therefore is not available for analysis.
Primary
Systemic Immune Response to HPV Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Lab results will be compared between patients who are HPV+ and HPV- using 2 sample t-tests. These measures will be compared in several ways. First, baseline, pre-treatment levels will be examined using descriptive statistics (n, mean, standard deviations, range). These measures will be examined overall and by HPV (+/-) groups. For each measure, and time point, 95% confidence intervals will be estimated. Next, two sample t-tests will be performed to compare levels of the measures at baseline. Next, measures taken post-treatment will be examined in a similar manner (descriptive statistics and 2-
Time frame: Up to 18 months
Population: This pre-specified outcome is dependent upon 1) patients having a measurable response and 2) availability of comparable cohorts of HPV positive and negative samples. Since there was a lack of measurable clinical response in all patients and the enrolled cohorts were unbalanced, the data for this outcome was not measured/evaluated and therefore is not available for analysis.
Primary
Systemic Immune Response to Tumor Associated Antigens Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Lab results will be compared between patients who are HPV+ and HPV- using 2 sample t-tests. These measures will be compared in several ways. First, baseline, pre-treatment levels will be examined using descriptive statistics (n, mean, standard deviations, range). These measures will be examined overall and by HPV (+/-) groups. For each measure, and time point, 95% confidence intervals will be estimated. Next, two sample t-tests will be performed to compare levels of the measures at baseline. Next, measures taken post-treatment will be examined in a similar manner (descriptive statistics and 2-
Time frame: Up to 18 months
Population: This pre-specified outcome is dependent upon 1) patients having a measurable response and 2) availability of comparable cohorts of HPV positive and negative samples. Since there was a lack of measurable clinical response in all patients and the enrolled cohorts were unbalanced, the data for this outcome was not measured/evaluated and therefore is not available for analysis.
Secondary
Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03
AEs will be coded using the Medical Dictionary for Regulatory Activities to their organ class by preferred term. Coded AEs will be displayed by frequency, severity, and relationship to treatment (durvalumab) in the safety population. In addition, summary tables will be generated for the following situations: 1) fatigue, diarrhea, nausea and skin rash; 2) Immune-mediated reactions of any grade; 3) other adverse events graded as 3 or more by CTCAE Version 4.03; 4) Durvalumab dose reductions; 5) discontinuations of treatment with durvalumab, with specification of reason for discontinuation; and 6) changes in the surgical treatment schedule. Toxicity grades Grade I (mild), Grade II (moderate), Grade III (severe), Grade IV (life threatening) and Grade V (fatal). Toxicities of greater than or equal to Grade III (except infusion reaction) are considered worse outcomes.
Time frame: At baseline (pre-treatment), during scheduled treatment and up to the 90-day follow up period after the last dose of study drug administered, with a median of 1 month and maximum of 13 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Constipation - Possible to Definitely relate - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alanine aminotransferase increased - Possible to Definitely related - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alanine aminotransferase increased - Possible to Definitely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alkaline phosphatase increased - Possible to Definitely related - Grade 1 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alkaline phosphatase increased - Possible to Definitely related - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Anemia - Unrelated or Unlikely related - Grade 3 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Anorexia - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Aspartate aminotransferase increased - Possible to Definitely related - Grade 1 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Aspartate aminotransferase increased - Possible to Definitely related - Grade 2 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Aspartate aminotransferase increased - Possible to Definitely related - Grade 4 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Blood bilirubin increased - Possible to Definitely related - Grade 1 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Blood bilirubin increased - Possible to Definitely relate - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Bullous dermatitis - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Constipation - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Acute kidney injury - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Device related infection - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Diarrhea - Possible to Definitely relate - Grade 1 | 3 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Diarrhea - Possible to Definitely relate - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Diarrhea - Unrelated or Unlikely related - Grade 1 | 4 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Possible to Definitely relate - Grade 1 | 6 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Possible to Definitely relate - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Unrelated or Unlikely related - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Unrelated or Unlikely related - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Head soft tissue necrosis - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hyperglycemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hyperglycemia - Unrelated or Unlikely related - Grade 4 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypermagnesemia - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypertension - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypoalbuminemia - Unrelated or Unlikely related - Grade 3 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypocalcemia - Unrelated or Unlikely related - Grade 3 | 4 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypocalcemia - Unrelated or Unlikely related - Grade 4 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypokalemia - Unrelated or Unlikely related - Grade 3 | 3 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hyponatremia - Unrelated or Unlikely related - Grade 3 | 4 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypophosphatemia - Unrelated or Unlikely related - Grade 3 | 4 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypotension - Unrelated or Unlikely related - Grade 3 | 2 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypothyroidism - Possible to Definitely relate - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Leukocytosis - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Lipase increased - Possible to Definitely relate - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Malaise - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Nausea - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Nausea - Unrelated or Unlikely related - Grade 1 | 3 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Neck soft tissue necrosis - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Neutrophil count decreased - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Pruritus - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Rash maculo-papular - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Rash pustular - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Serum amylase increased - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Skin ulceration - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Skin ulceration - Unrelated or Unlikely related - Grade 4 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Taste alteration (dysgeusia) - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Urine output decreased - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Urticaria - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Weight loss - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Wound complication - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Wound infection - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Discontinuation of Durvalumab due to immune-related hepatitis | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Weight loss - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Acute kidney injury - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypoalbuminemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alanine aminotransferase increased - Possible to Definitely related - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Neutrophil count decreased - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alanine aminotransferase increased - Possible to Definitely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypocalcemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alkaline phosphatase increased - Possible to Definitely related - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Taste alteration (dysgeusia) - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Alkaline phosphatase increased - Possible to Definitely related - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypocalcemia - Unrelated or Unlikely related - Grade 4 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Anemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Pruritus - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Anorexia - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypokalemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Aspartate aminotransferase increased - Possible to Definitely related - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Wound infection - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Aspartate aminotransferase increased - Possible to Definitely related - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hyponatremia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Aspartate aminotransferase increased - Possible to Definitely related - Grade 4 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Rash maculo-papular - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Blood bilirubin increased - Possible to Definitely related - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypophosphatemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Blood bilirubin increased - Possible to Definitely relate - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Urine output decreased - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Bullous dermatitis - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypotension - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Constipation - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Rash pustular - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Constipation - Possible to Definitely relate - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypothyroidism - Possible to Definitely relate - Grade 2 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Device related infection - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Wound complication - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Diarrhea - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Leukocytosis - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Diarrhea - Possible to Definitely relate - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Serum amylase increased - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Diarrhea - Unrelated or Unlikely related - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Lipase increased - Possible to Definitely relate - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Possible to Definitely relate - Grade 1 | 3 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Urticaria - Possible to Definitely relate - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Possible to Definitely relate - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Malaise - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Unrelated or Unlikely related - Grade 1 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Skin ulceration - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Fatigue - Unrelated or Unlikely related - Grade 2 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Nausea - Possible to Definitely relate - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Head soft tissue necrosis - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Discontinuation of Durvalumab due to immune-related hepatitis | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hyperglycemia - Unrelated or Unlikely related - Grade 3 | 1 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Nausea - Unrelated or Unlikely related - Grade 1 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hyperglycemia - Unrelated or Unlikely related - Grade 4 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Skin ulceration - Unrelated or Unlikely related - Grade 4 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypermagnesemia - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Neck soft tissue necrosis - Unrelated or Unlikely related - Grade 3 | 0 events |
| Treatment (Durvalumab, Surgery) - HPV Positive | Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03 | Hypertension - Unrelated or Unlikely related - Grade 3 | 1 events |
Secondary
Standardized Uptake Value (SUV) as Measured by PET Scans
Change in SUV activity as measured by PET scans from baseline to post-treatment not specific to HPV status.
Time frame: Up to 18 months
Population: This pre-specified outcome is dependent upon 1) patients having a measurable response and 2) availability of comparable cohorts of HPV positive and negative samples. Since there was a lack of measurable clinical response in all patients and the enrolled cohorts were unbalanced, the data for this outcome was not measured/evaluated for all patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Durvalumab, Surgery) | Standardized Uptake Value (SUV) as Measured by PET Scans | -0.15 change in SUV | Standard Error 1.2 |
| Treatment (Durvalumab, Surgery) - HPV Positive | Standardized Uptake Value (SUV) as Measured by PET Scans | 0 change in SUV | Standard Error 0 |
Secondary
Tumor Diameter Assessed Using RECIST Version 1.1 Criteria
Change in tumor diameters will be compared between groups (HPV +/-) pre- and post- treatment.
Time frame: Up to 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Durvalumab, Surgery) | Tumor Diameter Assessed Using RECIST Version 1.1 Criteria | 1.0 mm |
| Treatment (Durvalumab, Surgery) - HPV Positive | Tumor Diameter Assessed Using RECIST Version 1.1 Criteria | -2.0 mm |