Neoplasms

All Conditions

Symptoms and General Pathology

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Recurrence

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Vaccines

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pBI-11 vaccine IM, TA-HPV vaccine IM, and pembrolizumab IV on study. Patients undergo CT or MRI and blood sample collection during screening and on study. Patients may undergo tumor biopsy during screening and on study.

DNA Vaccine

Human Papillomavirus Tumor Antigen Vaccine

Computed Tomography (CT)

Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging

Biopsy

Vanderbilt-Ingram Services for Timely Access

Vanderbilt-Ingram Service for Timely Access

Michael Gibson, MD, PhD

This phase II trial tests how well pB1-11 and human papillomavirus tumor antigen (TA-HPV) vaccines in combination with pembrolizumab work in treating patients with oropharyngeal cancer that has come back (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic) and that is PD-L1 and human papillomavirus (HPV) positive. Oropharyngeal cancer is a type of head and neck cancer involving structures in the back of the throat (the oropharynx), such as the non-bony back roof of the mouth (soft palate), sides and back wall of the throat, tonsils, and back third of the tongue. Scientists have found that some strains or types of a virus called HPV can cause oropharyngeal cancer. pBI-11 is a circular deoxyribonucleic acid (DNA) (plasmid) vaccine that promotes antibody, cytotoxic T cell, and protective immune responses. TA-HPV is an investigational recombinant vaccina virus derived from a strain of the vaccina virus which was widely used for smallpox vaccination. Vaccination with this TA-HPV vaccine may stimulate the immune system to mount a cytotoxic T cell response against tumor cells positive for HPV, resulting in decreased tumor growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread by inhibiting the PD-1 receptor. These investigational vaccines could cause or enhance an immune response in the body against HPV, during which time the activity of pembrolizumab against oropharyngeal cancer associated with HPV may be strengthened. These drugs in combination may be more effective in increasing the ability of the immune system to fight oropharyngeal cancer than pembrolizumab alone.

PRIMARY OBJECTIVE:

I. To assess the safety and feasibility of intramuscular PVX7 (pBI-11/pBI-11/human papillomavirus tumor antigen vaccine \[TA-HPV\]) immunization in patients with HPV+ recurrent/metastatic (R/M) oropharyngeal carcinoma (OPC) undergoing treatment with pembrolizumab.

SECONDARY OBJECTIVE:

I. To assess the response rate (RR) of the addition of pBI-11 and TA-HPV to pembrolizumab (P) as first line therapy for patients with PD-L1+ (combined positive score \[CPS\] \>= 1), HPV+, R/M OPC.

EXPLORATORY OBJECTIVES:

I. To evaluate the overall survival (OS), progression free survival (PFS) and safety of the combination of PVX7 and pembrolizumab in this population.

II. To evaluate correlates of clinical activity by: (1) comparing HPV16/18 E6/E7-specific cellular and humoral immunity in pre- versus (vs.) post-pBI-11 and TA HPV-treated OPC patients that are pembrolizumab responders (R) and/or non-responders (NR).

OUTLINE:

Patients receive pBI-11 vaccine intramuscularly (IM), TA-HPV vaccine IM, and pembrolizumab intravenously (IV) on study. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on study. Patients may undergo tumor biopsy during screening and on study.

pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer

An Open-Label Phase II Clinical Trial Assessing the Safety, Feasibility, Efficacy and Immunological Correlates of Heterologous Prime-Boost With pBI-11 (IM) and TA-HPV (IM) Combined With Pembrolizumab as Treatment for Patients With Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer

The proportion of eligible, response evaluable patients with a best overall response (BOR). Objective response rate will be summarized as proportions of the total number of eligible, response evaluable patients with 95% confidence intervals. Logistic and Cox (proportional hazards) regression will be used to assess the association between important prognostic variables (e.g, gender, age) with objective response rate. Objective response rate will be monitored using Simon's minimax design.

The proportion of eligible, response evaluable patients with a best overall response of complete response, partial response or stable disease. Disease control rate will be summarized as proportions of the total number of eligible, response evaluable patients with 95% confidence intervals.

Estimated using the method of Kaplan and Meier (product limit estimator). Logistic and Cox (proportional hazards) regression will be used to assess the association between important prognostic variables (e.g, gender, age) with progression-free survival. The odds ratio (OR) for response and hazard ratio (HR) for progression-free survival will be presented with 95% confidence intervals as measure of effect size.

Estimated using the method of Kaplan and Meier (product limit estimator). Logistic and Cox (proportional hazards) regression will be used to assess the association between important prognostic variables (e.g, gender, age) with overall survival. The odds ratio for response and hazard ratio for overall survival will be presented with 95% confidence intervals as measure of effect size.

Michael K. Gibson

Associate Professor of Medicine

Respiratory Tract (Lung and Bronchial) Diseases

Musculoskeletal Diseases

Rare Diseases

Laryngeal Neoplasms

Paranasal Sinus Neoplasms

Disease Attributes

Laryngeal Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Nose Neoplasms

Nose Diseases

Paranasal Sinus Diseases

Laryngeal Cancer

Hypopharyngeal Cancer

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Pyrazole

Celecoxib

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Patients receive celecoxib PO or via feeding tube BID starting 1 to 7 days prior to surgery and continues until the completion of radiation therapy (up to 6 months in total) in the absence of disease progression or unacceptable toxicity.

Patients receive placebo PO or via feeding tube BID starting 1 to 7 days prior to surgery and continues until the completion of radiation therapy (up to 6 months in total) in the absence of disease progression or unacceptable toxicity.

Placebo

Quality-of-Life Assessment

Questionnaire Administration

Richard Cannon, MD

This phase II trial studies how well celecoxib works through surgery and radiation therapy in treating patients with head and neck cancer that has spread to other places in the body (advanced). Celecoxib is Food and Drug Administration approved to treat arthritis, acute pain, and painful menstrual periods. Adding celecoxib to standard of care treatment may help to decrease the amount of time between surgery and radiation therapy.

PRIMARY OBJECTIVE:

I. To assess the number of days from surgery to initiation of radiation with the addition of celecoxib compared to placebo.

SECONDARY OBJECTIVES:

I. To assess overall pain control and management for patients on celecoxib compared to placebo.

II. To assess functional outcomes for patients on celecoxib compared to placebo.

III. To assess the effect of celecoxib therapy on Quality of Life (QoL) compared to placebo.

IV. To assess the average number of treatment days missed during adjuvant radiation for patients on celecoxib compared to placebo.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive celecoxib orally (PO) or via feeding tube twice daily (BID) starting 5 days prior to surgery and continues until the completion of radiation therapy (up to 6 months in total) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO or via feeding tube BID starting 5 days prior to surgery and continues until the completion of radiation therapy (up to 6 months in total) in the absence of disease progression or unacceptable toxicity.

Celecoxib Through Surgery and Radiation Therapy for the Treatment of Advanced Head and Neck Cancer

RESILIENCE: Effect of Comprehensive Celecoxib Through Treatment for Advanced-Stage Head and Neck Cancer: A Randomized, Double-Blinded, Placebo-Controlled Trial

The day of surgery will be considered day 0 and the number of days will be counted until the first dose of adjuvant radiation. A Gaussian mixed effects regression model will be used to compare the average number of days from surgery to the initiation of radiation and adjuvant therapy between treatment and control groups. The model will contain fixed effects for treatment arm and provider and a nested random effect for patient within provider. The mean difference between treatment groups, two-sided p-value and 95% confidence interval will be calculated from the model.

Assessment of subjective pain scores on the visual analog scale of pain intensity averaged over a week at rest, with a swallow, and with a cough. Pain intensity scale is a range from 0-10. 0= No Pain, 5= Moderate pain, 10= Unbearable paining

Assessment of current activity level and swallowing capabilities, including food and liquid variety and assessment of G tube utilization.

Completion of quality of life questionnaire EORTC QLQ-H\&N43 as per the protocol described schedule.

Assess the number of treatment days missed or delayed during adjuvant radiation.

Narcotic consumption will be assessed in daily total morphine equivalents averaged over a week

Patient satisfaction will be assessed with pain control questionnaire.

Completion of quality of life questionnaire MDASI-HN as per the protocol described schedule.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer	NCT05799144	Metastatic Orop... Recurrent Oroph...	DNA Vaccine Human Papilloma... Pembrolizumab Computed Tomogr... Magnetic Resona... Magnetic Resona... Biopsy	18 Years -	Vanderbilt-Ingram Cancer Center
pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer	NCT05799144	Metastatic Orop... Recurrent Oroph...	DNA Vaccine Human Papilloma... Pembrolizumab Computed Tomogr... Magnetic Resona... Magnetic Resona... Biopsy	18 Years -	Vanderbilt-Ingram Cancer Center
Celecoxib Through Surgery and Radiation Therapy for the Treatment of Advanced Head and Neck Cancer	NCT04162873	Clinical Stage ... Clinical Stage ... Nasal Cavity an... Oral Cavity Car... Pathologic Stag... Pathologic Stag... Recurrent Hypop... Recurrent Laryn... Recurrent Nasal... Recurrent Oral ... Recurrent Oroph... Stage III Hypop... Stage III Laryn... Stage III Oroph... Stage IV Hypoph... Stage IV Laryng... Stage IV Oropha... Stage IVA Hypop... Stage IVA Laryn... Stage IVA Oroph... Stage IVB Hypop... Stage IVB Laryn... Stage IVB Oroph... Stage IVC Hypop... Stage IVC Laryn... Stage IVC Oroph...	Celecoxib Placebo Quality-of-Life... Questionnaire A...	18 Years -	University of Utah

Spots Global Cancer Trial Database for recurrent oropharyngeal carcinoma