Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Head and Neck Neoplasms

Laryngeal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over at least 30 minutes every 2 weeks and ipilimumab IV over at least 90 minutes every 6 weeks. Beginning week 3, patients undergo simultaneous integrated boost intensity modulated radiation therapy or volumetric modulated arc therapy for 5 days per week over 7 weeks. Patients continue nivolumab every 2 weeks for 12 doses and ipilimumab every 6 weeks for 4 doses. Courses repeat for up to 23 weeks in the absence of disease progression or unacceptable toxicity.

Undergo simultaneous integrated boost integrated modulated radiation therapy

Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy

Volume Modulated Arc Therapy

Jennifer Johnson, MD, PhD

This pilot clinical trial studies the side effects of nivolumab, ipilimumab and radiation therapy in treating patients with stage IVA-B head and neck cancer. Monoclonal antibodies, such as nivolumab and ipilimumab, 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 nivolumab, ipilimumab, and radiation therapy may work better in treating patients with stage IVA-B head and neck cancer.

PRIMARY OBJECTIVES:

I. To investigate the safety of the combination of nivolumab and ipilimumab with radiation treatment for definitive management of patients with locally advanced squamous cell carcinoma of the head and neck.

SECONDARY OBJECTIVES:

I. To estimate the 1 year progression-free survival (PFS) in all patients treated.

II. To assess the overall response rate and overall survival of patients at one year

TERTIARY OBJECTIVES:

I. To explore whether PDL1 expression is associated with treatment response. II. To explore whether there is a net change in the Th1/Th2 ratio (IFN-gamma, IL-4, IL10, etc) or cell subset frequencies (M2 monocytes, myeloid-derived suppressor cells, etc) within a patient's peripheral blood either at baseline or in response to treatment is associated with treatment response.

III. To explore whether exosomes or other immune related serum biomarkers change after combination therapy.

Nivolumab, Ipilimumab, and Radiation Therapy in Treating Patients With Stage III-IVB Head and Neck Cancer

A Pilot Trial of Nivolumab and Ipilimumab in Combination With Radiotherapy in Patients With Locally Advanced Head and Neck Cancer; CA209-931

There will be continuous monitoring of the incidence of grade 3-5 toxicities.

Bristol-Myers Squibb

Sidney Kimmel Cancer Center at Thomas Jefferson University

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Vasodilator Agents

Urological Agents

Tadalafil

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Patients receive nivolumab IV over 60 minutes on days 3 and 17 and undergo surgery on day 31.

Patients receive nivolumab IV over 60 minutes on days 3 and 17 and tadalafil PO QD on days 3-31. Patients then undergo surgery on day 31.

Therapeutic Conventional Surgery

Adam Luginbuhl, MD

This randomized pilot early phase I trial studies how well nivolumab with or without tadalafil work in treating patients with head and neck squamous cell carcinoma that has come back and can be removed by surgery. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Tadalafil may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab and tadalafil may work better in treating patients head and neck squamous cell carcinoma.

PRIMARY OBJECTIVES:

I. To investigate whether adding the PDE5 inhibitor, tadalafil, to nivolumab therapy affects intratumoral and systemic anti-tumor immunity.

SECONDARY OBJECTIVES:

I. Characterize the combined effects of nivolumab and tadalafil on safety, exosome composition and function, the composition of intratumoral immune cell populations, wound healing, and tumor radiographic response.

Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck

Analyze the immune cell polarization (Th1/Th2; M1/M2) in peripheral blood and tumor specimen supernatants will look at an entire panel of inflammatory markers, utilizing Luminex technology with the milliplex MAP human cytokine/chemokine magnetic kit I

We will use immunohistochemistry (IHC) to determine the prevalence of intratumoral immune cell populations in patients treated with nivolumab and tadalafil as compared to patients treated with nivolumab alone.

Patients undergo FBCT once before treatment and once weekly for a total of 6-7 scans, dual CBCT up to 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian kV OBI 5 times weekly for a total of 33-35 scans, 2-D x-ray with Brain Lab ExacTrac 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian MV OBI once weekly for a total of 6-7 scans, and EPID imaging up to 5 times weekly for a total of 33-35 scans while undergoing IGART.

computed tomography

cone-beam computed tomography

radiography

Undergo 2-D x-ray with Brain Lab ExacTrac

electronic portal imaging

image-guided adaptive radiation therapy

Joshua Evans, PhD

This clinical trial studies image-guided adaptive radiotherapy in detecting tumors during treatment in patients with head and neck cancer. Image-guided adaptive radiotherapy uses high quality imaging technology to detect the tumor and normal organs during treatment. It is not yet known which imaging technique provides the best image for guidance during treatment with radiation therapy. Comparing results of imaging procedures done before, during, and after radiotherapy may help doctors plan the best treatment.

I. To conduct a clinical imaging study utilizing three novel in-room imaging systems: Oblique Brainlab ExacTrac images, Orthogonal Varian kilovoltage (kV) On-board Imaging (OBI) image, and Varian cone-beam computed tomography (CBCT) imaging to assess their performance in reducing inter- and intrafractional setup errors, relative to weekly megavoltage (MV) electronic portal imaging device (EPID) images, using both bony landmarks and soft tissue changes for head and neck cancer (HNC) patients undergoing external beam radiation therapy (RT).

II. To assess the accuracy of CBCT imaging for measuring systematic soft tissue changes in the head and neck (HN) area relative to conventional high resolution contrast enhanced fan-beam computed tomography (CT) (FBCT) as a standard.

III. To assess the systematic and random soft tissue motion errors using daily CBCT imaging relative to bony-landmark alignment to evaluate the benefit of soft tissue imaging during radiotherapy.

IV. To quantify soft tissue changes during an entire course of radiotherapy (e.g. tumor shrinkage) using daily CBCT imaging.

V. To determine the feasibility of using measured set up and soft-tissue motion uncertainties in conjunction with volume changes observed on serial CBCT images, for offline adaptive replanning of HNC patients using available planning tools.

VI. To quantify the benefits of adaptive image-guided radiotherapy (IGRT) in HN patients in terms of target coverage and normal tissue avoidance.

VII. To determine the feasibility of mounting a phase I/II trial to assess the clinical benefits of image-guided adaptive radiotherapy (IGART) in terms of acute and late toxicities and tumor control.

VIII. To build a HNC patient database for future validation of IGART processes using deformable image registration and Virtual Clinical Trials (VCTs).

OUTLINE:

Patients undergo FBCT once before treatment and once weekly for a total of 6-7 scans, dual CBCT up to 5 times weekly for a total of 33-35 scans, 2-dimensional (2-D) x-ray with Varian kV OBI 5 times weekly for a total of 33-35 scans, 2-D x-ray with Brain Lab ExacTrac 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian MV OBI once weekly for a total of 6-7 scans, and EPID imaging up to 5 times weekly for a total of 33-35 scans while undergoing IGART.

Image-Guided Adaptive Radiotherapy for in Detecting Tumors During Treatment in Patients With Head and Neck Cancer

Image-Guided Adaptive Radiotherapy for Head And Neck Cancer: Patient Image Acquisition

The automated patient setup procedure varies between 'OBI', 'CBCT' or 'Exactrac' imaging technologies. Each procedure gives two shifts: 'vertical' and 'lateral'. In the absence of a gold standard, our goal is to compare the shifts recommended by each pair of automated patient setup procedures. Average and Std deviation of vertical and lateral motion from the three systems were computed. P value, 1.00, refers to the test of difference of each system with OBI being more than 2 mm. Pairwise comparison for each direction between each pair of technologies were done using a t test to check if the difference in the recommended shift is more than 2 mm. The reported mean value represents the shift from planned treatment position averaged over all daily treatment setups. A negative mean vertical value indicates the patient was consistently set up posterior to plan; a negative mean lateral value indicates a set up consistently right of plan.

Virginia Commonwealth University

Patients undergo FBCT once before treatment and once weekly for a total of 6-7 scans, dual CBCT up to 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian kV OBI 5 times weekly for a total of 33-35 scans, 2-D x-ray with Brain Lab ExacTrac 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian MV OBI once weekly for a total of 6-7 scans, and EPID imaging up to 5 times weekly for a total of 33-35 scans while undergoing IGART.

computed tomography: Undergo FBCT

cone-beam computed tomography: Undergo dual CBCT

radiography: Undergo 2-D x-ray with Varian kV OBI

radiography: Undergo 2-D x-ray with Brain Lab ExacTrac

radiography: Undergo 2-D x-ray with Varian MV OBI

electronic portal imaging: Undergo EPID imaging

image-guided adaptive radiation therapy: Undergo IGART

Diagnostic (Imaging Technology)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Joshua Evans, Ph.D.

Pairwise comparison for each direction between each pair of technologies were done using a t test to check if the difference in the recommended shift is more than 2 mm. Clinical significance is based on a 2 mm difference. Statistical significance is determined based on 5% level of significance.

Vertical shift

Lateral shift

Patients are first set up for treatment with surface fiducial marks and followed by an automated image guided alignment procedure to achieve better alignment with the planning image. The automated procedure OBI gives two shifts: vertical and lateral. In the absence of a gold standard, our goal is to compare the vertical and lateral shifts recommended by each pair of automated procedures.

Orthogonal Varian kV OBI Image

Patients are first set up for treatment with surface fiducial marks and followed by an automated image guided alignment procedure to achieve better alignment with the planning image. The automated procedure CBCT gives two shifts: vertical and lateral. In the absence of a gold standard, our goal is to compare the vertical and lateral shifts recommended by each pair of automated procedures.

Varian CBCT (Cone Beam CT) Imaging

Patients are first set up for treatment with surface fiducial marks and followed by an automated image guided alignment procedure to achieve better alignment with the planning image. The automated procedure ExacTrac gives two shifts: vertical and lateral. In the absence of a gold standard, our goal is to compare the vertical and lateral shifts recommended by each pair of automated procedures.

Oblique Brainlab ExacTrac Images

Ten evaluable head and neck patients treated with external beam radiation therapy received 19 to 32 fractions with all three imaging techniques. The mean daily shift of these 19 to 32 fractions were recorded for each technique. Statistical significance is determined based on 5% level of significance.

Differences of Calculated Set up Errors of 2 mm Between the Different Imaging Technologies

No data analyzed due to staff leaving primary institution.

Dose Variation Between the Different Imaging Technologies for Normal Tissue Structures of 10%

Greater Than or Equal to 5% Variation of Normal Tissue Toxicity

Patients undergo FBCT once before treatment and once weekly for a total of 6-7 scans, dual CBCT up to 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian kV OBI 5 times weekly for a total of 33-35 scans, 2-D x-ray with Brain Lab ExacTrac 5 times weekly for a total of 33-35 scans, 2-D x-ray with Varian MV OBI once weekly for a total of 6-7 scans, and EPID imaging up to 5 times weekly for a total of 33-35 scans while undergoing IGART.

computed tomography: Undergo FBCT cone-beam computed tomography: Undergo dual CBCT radiography: Undergo 2-D x-ray with Varian kV OBI radiography: Undergo 2-D x-ray with Brain Lab ExacTrac radiography: Undergo 2-D x-ray with Varian MV OBI electronic portal imaging: Undergo EPID imaging image-guided adaptive radiation therapy: Undergo IGART

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab, Ipilimumab, and Radiation Therapy in Treating Patients With Stage III-IVB Head and Neck Cancer	NCT03162731	Larynx Lip, Oral Cavit...	Nivolumab Ipilimumab Simultaneous-In... Volume Modulate...	18 Years -	Thomas Jefferson University
Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck	NCT03238365	Lip, Oral Cavit... Larynx	Nivolumab Tadalafil Therapeutic Con...	18 Years -	Thomas Jefferson University
Image-Guided Adaptive Radiotherapy for in Detecting Tumors During Treatment in Patients With Head and Neck Cancer	NCT01843673	Head and Neck C...	computed tomogr... cone-beam compu... radiography radiography radiography electronic port... image-guided ad...	21 Years -	Virginia Commonwealth University

Spots Global Cancer Trial Database for lip, oral cavity and pharynx