Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.

Intensity-Modulated Radiation Therapy

Quality-of-Life Assessment

Questionnaire Administration

Maura Gillison

Maura L. Gillison

Maura L Gillison

This phase II trial studies the side effects and best dose of ipilimumab, nivolumab, and radiation therapy and how well they work in treating patients with advanced human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving ipilimumab, nivolumab, and radiation therapy may work better in treating patients with HPV positive oropharyngeal squamous cell carcinoma.

PRIMARY OBJECTIVES:

I. To evaluate the safety, tolerability and feasibility of ipilimumab and nivolumab when administered concurrently with reduced-field radiotherapy (intensity-modulated radiation therapy \[IMRT\]).

II. To evaluate the clinical complete response rate to ipilimumab, nivolumab and IMRT with reduced field at six months as indicated by fluorodeoxyglucose - positron emission tomography/computed tomography (FDG-PET/CT) post completion of radiation therapy (RT).

III. To evaluate the 2-year progression-free survival (PFS) rate of subjects with low-intermediate volume, local-regionally advanced, human papilloma virus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) treated with ipilimumab, nivolumab and reduced-field IMRT.

SECONDARY OBJECTIVES:

I. To evaluate overall response rate to six weeks of induction immunotherapy (IO).

II. To evaluate the frequency of pharyngeal dysphasia as measured by Dynamic Imaging (Dynamic Imaging Grade of Swallowing Toxicity \[DIGEST\]) grade on modified barium swallow (MBS) and patient-reported symptoms (MD Anderson Dysphagia Inventory \[MDADI\]) at 6 month, 1 and 2 years after radiotherapy (\[IMRT\].

III. To measure acute and chronic toxicities per Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (CTCAE PRO).

IV. To measure acute toxicity profiles at the end of radiation therapy and IO and at 6 months.

V. To measure late toxicity profiles at 1 and 2 years. VI. To determine local and regional control at 6 and 12 months. VII. To determine patterns of failure (local-regional relapse vs. distant) at 1 and 2 years.

VIII. To determine overall survival (OS) at 1 and 2 years.

CORRELATIVE OBJECTIVES:

I. To evaluate associations between total mutational load, interferon (INF) gamma score, T cell clonality at diagnosis with clinical response to induction, combination CTLA-4 PD-1 checkpoint blockade.

II. To evaluate changes in the tumor immune microenvironment (CD8 + INF gamma score, T cell clonality, in tumor biopsy specimens pre and post induction immunotherapy (IO).

III. To evaluate dynamic changes in and clearance of oral HPV and cell-free deoxyribonucleic acid (cfDNA) viral load during therapy and to investigate associations with PFS and OS.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in peripheral blood lymphocyte phenotypes and serum cytokine profiles before and after induction IO.

II. To evaluate changes in the T cell receptor repertoire in tumor-infiltrating lymphocyte (TIL) and the peripheral blood in tumor biopsy specimens pre and post induction IO.

III. To determine the negative and positive predictive values (NPV and PPV) of FDG-PET/CT 12-14 weeks after end of RT for 1 year and 2 year PFS and OS.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Ipilimumab, Nivolumab, and Radiation Therapy in Treating Patients With HPV Positive Advanced Oropharyngeal Squamous Cell Carcinoma

Phase 2 Study (With Safety Lead in) of the Safety, Tolerability and Efficacy of Anti-CTLA4 (Ipilimumab) and Anti-PD-1 (Nivolumab) in Combination With Radiation Therapy to 50-66 Gy in Low-Intermediate Volume, Local-Regionally Advanced HPV-Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Defined as any \>= grade 3 adverse event (Common Terminology Criteria for Adverse Events \[CTCAE\], version \[v.\] 4) that is related to immunotherapy (IO) that does not resolve to grade 1 or less within 28 days.

The number of patients who tolerated protocol therapy, including completion of radiotherapy without a treatment break and who were administered immunotherapy (IO) will be assessed.

Incidence of adverse events (acute and chronic toxicities) will be assessed per CTCAE Patient Reported Outcome (PRO).

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Rare Diseases

Tonsillar Neoplasms

Tongue Cancer

Antihypertensive Agents

Brimonidine Tartrate

Patients with either known or suspected oropharyngeal cancer will be asked to undergo a transcervical ultrasound and to provide a blood and oral rinse specimen.

One time approximately 15 minute ultrasound will be conducted at the time of clinic visit, focusing on the base of tongue and palatine tonsil via transcervical approach.

Transcervical Oropharyngeal Ultrasound

Patients will provide a one time oral rinse specimen using a non-alcoholic mouthwash at the time of clinic visit. The participant will be instructed to swish vigorously for 5 seconds and then gargle 5 seconds. The participant will be asked to repeated the swish and gargle (5 seconds each) three times for a total of 30 seconds and then expel the wash in a 10mL conical tube.

Oral Rinse Collection

A certified phlebotomist will perform a one time blood draw of 10mL at the time of clinic visit from each participant for purposes of HPV serologic testing.

Blood Draw

Krystle A Kuhs, PhD

Background: The incidence of human papilloma virus-driven oropharyngeal cancer (HPV-OPC), a type of head and neck cancer, is rapidly increasing within the US. Currently, there are no screening methods for early detection. HPV16 E6 antibodies combined with ultrasound imaging may be a promising method for early detection of HPV-OPC. However, prior to testing HPV16 E6 antibodies and ultrasound for HPV-OPC screening, larger studies are needed to further validate the utility of these methods in the diagnostic setting among patients with suspected and/or symptomatic HPV-OPC.

Objective/Hypothesis: To investigate two promising screening modalities for the detection of HPV-OPC, transcervical ultrasound and HPV16 E6 antibodies. The investigators hypothesize that both ultrasound and HPV16 E6 antibodies will be highly sensitive for the detection of symptomatic HPV-OPC.

Specific Aims: (1) Determine the sensitivity of ultrasound to characterize OPC tumors compared to current standard imaging modalities among patients with suspected or confirmed OPC. (2) To determine the sensitivity and specificity of HPV16 E6 antibodies for HPV-OPC. (3) Determine the sensitivity of ultrasound to detect HPV-OPC compared to current standard imaging modalities among patients that present with a neck mass and unknown primary tumor.

50 patients with suspected or confirmed OPC will undergo a transcervical ultrasound during their first visit at the Vanderbilt Head and Neck Clinic in addition to other imaging modalities (CT, MRI and/or PET) as indicated as part of routine clinical care; patients will also be asked to provide a blood specimen. Ultrasound exams will be performed by a clinician blinded to details of the case. All patients will have a CT as part of their diagnostic work-up. Sensitivity of ultrasound to detect tumors identified by CT will be determined. Approximately 40% of patients are expected to test negative on CT requiring MRI and/or PET imaging. Among this subset, the sensitivity of ultrasound to detect tumors identified by either PET and/or MRI will be determined. Tumor size will be determined by 3 ultrasound measurements along the largest diameter of the tumor; agreement between ultrasound and the clinical imaging modalities will be calculated. The investigators will recruit an additional 78 OPC patients with pre-treatment serum banked within the Vanderbilt Head and Neck Cancer Biorepository (18 HPV-negative, 60 HPV-OPC) for HPV serologic analyses; total: 128 samples. Sensitivity and specificity of HPV16 E6 antibodies for detecting HPV-OPC will be calculated. As an exploratory aim, the proportion of tumors undetectable by CT, PET, and MRI, but detected by ultrasound will be determined.

Investigators conducting the ultrasound study will be masked as to the characteristics/location of patient's tumor in order to determine feasibility of identifying oropharyngeal cancers as a sole imaging technique.

New Modalities for Detection of Oropharyngeal Cancer

Advancing New Modalities for the Detection of Oropharyngeal Cancer: Transcervical Ultrasound and HPV16 E6 Antibodies

Ability to detect oropharyngeal tumor via ultrasound will be a primary outcome of the study. Characteristics including ability to detect tumor, tumor size, and tumor location will be recorded at time of ultrasound. The ultrasound findings will then be compared to other imaging modalities used as standard work-up (CT/MRI). This comparison will be used to determine sensitivity of ultrasound for detection of oropharyngeal tumors.

Both serum samples and oral rinse specimens will be shipped to German Cancer Research Center, Heidelberg (DKFZ) for blinded analysis of HPV antibodies. The samples will be completely de-identified prior to shipment and thus, there will be no way for the testing laboratory to link the specimens back to the patients. A random sample of blinded duplicates (10%) will be included as part of quality control. Seroreactivity against the HPV16 E6 protein will be determined using multiplex serology, an antibody detection method based on a glutathione S-transferase capture ELISA in combination with fluorescent bead technology.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ipilimumab, Nivolumab, and Radiation Therapy in Treating Patients With HPV Positive Advanced Oropharyngeal Squamous Cell Carcinoma	NCT03799445	Clinical Stage ... Clinical Stage ... Human Papilloma... Oropharyngeal B... Pathologic Stag... Pathologic Stag... Posterior Tongu... Soft Palate Squ... Stage III Oroph... Stage IVA Oroph... Tonsillar Squam...	Intensity-Modul... Ipilimumab Nivolumab Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
New Modalities for Detection of Oropharyngeal Cancer	NCT03226613	Human Papilloma... Oropharynx Canc... Base of Tongue ... Tonsil Cancer	Transcervical O... Oral Rinse Coll... Blood Draw	21 Years -	Vanderbilt University Medical Center
New Modalities for Detection of Oropharyngeal Cancer	NCT03226613	Human Papilloma... Oropharynx Canc... Base of Tongue ... Tonsil Cancer	Transcervical O... Oral Rinse Coll... Blood Draw	21 Years -	Vanderbilt University Medical Center

Spots Global Cancer Trial Database for human papillomavirus positive oropharyngeal squamous cell carcinoma