Research & Innovation

Head and Neck Clinical Trials

Clinical Trials

Biothera BT-CL-PGG-HNC-1622 / MK3475 PN-544

A Multicenter, Open-label, Phase 2 Study of Imprime PGG and Pembrolizumab in Subjects with Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) Who Have Failed Pembrolizumab Monotherapy or Who Are Actively Experiencing Stable Disease Following Completion of at Least 4 Cycles, but No More than 8 Cycles, of Pembrolizumab Monotherapy

Physician & Study Coordinator

Study Coordinator

Jillian Timer, RN, BSN
484-503-4156 

Jillian.timer@sluhn.org

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Synopsis

Treatment Agent: Pembrolizumab, Imprime PGG Injection

Synopsis: The purpose of this study is to find out good and/or bad effects of the investigational drug, Imprime PGG, when given together with pembrolizumab in the treatment of your type of cancer. An investigational drug is one that is not approved by the United States Food and Drug Administration (FDA). Imprime PGG is a glucan. Glucans are molecules that are not normally present in your body. Imprime PGG when given with pembrolizumab may help the immune system to fight your type of cancer. Pembrolizumab is already approved by the FDA when given alone for the treatment of advanced metastatic melanoma, non-small cell lung cancer, and in recurrent or metastatic SCCHN for patients with disease progression on or after platinum-containing chemotherapy. The combination of these drugs used in this study is also investigational.

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Inclusion Criteria
  • Have signed an informed document prior to any study-specific procedures or treatment
  • Be ≥ 18 years of age at time of consent
  • Have histologically or cytologically confirmed diagnosis of SCCHN irrespective of PD-L1 status, which is either inoperable and recurrent, or metastatic
  • Up to 3 prior chemotherapy regimens or metastatic disease
  • Have either:
    • Investigator determined assessment of disease progression after treatment with pembrolizumab monotherapy, OR
    • Investigator determined assessment of current stable disease following completion of at least 4 cycles but no more than 8 cycles, of pembrolizumab monotherapy
  • Have resolution of all previous treatment-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2) or alopecia. If subject received major surgery or radiation therapy of > 30 Gy, must have recovered from the toxicity and/or complications from the intervention.
  • Have at least one radiologically measurable lesion as per RECIST v1.1 defined as a lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or MRI and obtained by imaging within 28 days prior to start of study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Have peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 mcg/mL as determined by an ELISA test within 90 days prior to start of study treatment
  • Be willing to consider providing fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality, for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded block specimens are preferred to slides.
    Note: Information on 1 tumor biopsy sample is mandatory and is as follows: (1) To determine eligibility, historical (diagnostic) tumor biopsy official pathology report +/- an archival sample. Additional biopsy samples, preferably obtained from the same localized region, are highly desirable when feasible at the following time points: (2) Sample before the first dose of study treatment, (3) Sample after completion of Cycle 2 but before the start of Cycle 3 dosing, and (4) Sample either at the time of response or at the End of Study Visit (if no response).
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 14.3)
  • Have life expectancy of 6 months or greater as determined by the treating physician
  • Have adequate organ function (all screening labs should be performed within 15 days prior to study treatment):
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN
    • Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
    • Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
    • Albumin level ≥3 g/dL
  • Have adequate renal function within 15 days prior to study treatment, defined by the following criteria: Creatinine ≤ 1.5 x ULN and CrCl ≥ 30 ml/min per Cockcroft Gault formula:
  • Have adequate hematologic function within 15 days prior to study treatment, defined as meeting all of the following criteria:
    • Hemoglobin ≥ 9 g/dL (uncorrected by RBC transfusion)
    • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
    • Platelet count ≥ 100 × 109/L
  • Have adequate coagulation functioning within 15 days prior to start of study treatment, defined by either of the following criteria:
    • INR < 1.5 × ULN
    • OR for subjects receiving warfarin or low molecular weight heparin (LMWH), the subjects must, in the Investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
    • Activated Partial Thromboplastin Time (aPTT) < 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subjects of childbearing potential as defined in Section 5.7.2 must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • If of childbearing potential as defined in Section 5.7.2, must be willing to use an adequate method of contraception (see Section 5.7.2) from the first dose of study medication through 120 days after the last dose of study medication
  • Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures

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Exclusion Criteria
  • Has disease that is suitable for local therapy administered with curative intent
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
  • Has known history of active tuberculosis
  • Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Has known active Hepatitis B (eg, HBsAg reactive) or Hepatitis C (eg, HCV RNA [qualitative] is detected
  • Has a history of clinically severe autoimmune disease, or history of organ transplant
  • Has known hypersensitivity to baker's yeast
  • Had previous exposure to Betafectin® or Imprime PGG
  • Has severe hypersensitivity to pembrolizumab or any of its excipients
  • Had a prior anti-cancer monoclonal antibody (other than pembrolizumab) within 30 days prior to start of study treatment, or failure to recover to CTCAE Grade 1 or better from the adverse events of prior therapies
  • Had within 2 weeks prior to the first dose of study treatment, received prior chemotherapy, targeted small molecule therapy, or radiation therapy, or who has not recovered from adverse events due to a previously administered agent or major surgery
  • Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF, or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment
  • Has known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Has active autoimmune disease requiring systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteriod replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has a history of interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator
  • Has a clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome within ≤180 days prior to start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Has a known psychiatric or substance abuse disorder(s) that would interfere with informed consent or cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted

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Enzychem EC-18-202

Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EC-18 in altering the severity and course of oral mucositis in patients being treated with concomitant chemoradiation therapy for cancers of the mouth, oropharynx, hypopharynx and nasopharynx

Physician & Study Coordinator

Study Coordinator

Jillian Timer, RN, BSN
484-503-4156 

Jillian.timer@sluhn.org

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Synopsis

Treatment Agent: EC-18

Synopsis: The purpose of Stage 1 of this research study is to measure the safety of the study drug EC-18 at different dosages in patients being treated with chemoradiation for cancers of the mouth, oropharynx, hypopharynx and nasopharynx.

Sometimes it is not known which way of treating patients is best. To find out, researchers need to compare different treatments. People are put into groups and each group given a different treatment. The results are compared to see if one is better. To try to make sure the groups are the same to start with, each patient is assigned to a group by chance (randomly). Stage 1 of this study, is called a “dose-finding” stage. This means that the dose level of the study drug EC-18 may be different for each patient. Twenty-four (24) patients will be equally randomized (divided) into 4 groups to receive a dosage of either EC-18 500 mg, EC-18 1000 mg, EC-18 2000 mg or placebo. A placebo is a medication which looks exactly like the investigational drug but has no active ingredient.  You, your study doctor and study staff will not know what dosage you are receiving or if you are receiving placebo. All the softgels look the same whether study medication or placebo.

The purpose of this study is to find out good and/or bad effects of the investigational drug, Imprime PGG, when given together with pembrolizumab in the treatment of your type of cancer. An investigational drug is one that is not approved by the United States Food and Drug Administration (FDA). Imprime PGG is a glucan. Glucans are molecules that are not normally present in your body. Imprime PGG when given with pembrolizumab may help the immune system to fight your type of cancer. Pembrolizumab is already approved by the FDA when given alone for the treatment of advanced metastatic melanoma, non-small cell lung cancer, and in recurrent or metastatic SCCHN for patients with disease progression on or after platinum-containing chemotherapy. The combination of these drugs used in this study is also investigational.

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Inclusion Criteria
  • Signed informed consent
  • Male or female age 21 years or older
  • Pathologically confirmed diagnosis of squamous cell carcinoma of the mouth, oropharynx, hypopharynx or nasopharynx
  • Planned to receive IMRT with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative dose of at least 60 Gy and a maximum of 72 Gy
  • Radiation fields to include at least two mucositis sites at risk (buccal mucosa, floor of mouth, ventral and lateral tongue, soft palate) in which both sites receive a minimum cumulative dose of 55 Gy
  • Planned to receive concomitant single agent chemotherapy with cisplatin given either weekly or tri-weekly
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  • Screening Laboratory Values Hemoglobin ≥ 9g/dL White blood cell count ≥ 3,500 cells/mm3 Absolute neutrophil count ≥ 1,500 cells/mm3 Total bilirubin ≤ 2 times upper limit of normal Serum AST and ALT ≤ 2.5 times upper limit of normal Serum creatinine concentration ≤ 2mg/mL Pregnancy test: negative for females of childbearing potential
  • Subjects of childbearing potential must consent to utilize a medically accepted means of contraception throughout the active dosing period with study medication and for a minimum of 30 days following the administration of the last dose of study medication.

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Exclusion Criteria

Unable to provide informed consent or, in the opinion of the Principal Investigator, comply with the protocol.

  • Prior radiation therapy to the head and neck
  • Metastatic disease
  • Presence of active infectious disease excluding oral candidiasis
  • Presence of oral mucositis or any oral lesion that would confound the assessment of oral mucositis
  • Active systemic disease or condition known to impact the risk or course of oral mucositis including chronic immunosuppression and known seropositivity for HIV
  • Use of any investigational agent within 30 days of the first radiation dose
  • Active alcohol abuse syndrome
  • Subjects with a history of hepatitis of any etiology or hepatic insufficiency
  • Pregnant or nursing at the time of signing informed consent
  • Known sensitivity to any study medication
  • Unwilling or unable to complete study diary
  • Any other condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the protocol

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Galera GTI-4419-301

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Superoxide Dismutase Mimetic GC4419 to Reduce Severe Oral Mucositis (SOM) Associated with
Chemoradiotherapy for Locally Advanced, Non-Metastatic Head and Neck Cancer

Physician & Study Coordinator

Study Coordinator

Jillian Timer, RN, BSN
484-503-4156 

Jillian.timer@sluhn.org

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Synopsis

Treatment Agent: GC4419

Synopsis: The main purpose of this study is to further investigate whether fewer people getting radiation therapy and chemotherapy for head and neck cancer will get severe oral mucositis if they get GC4419 along with chemoradiation.  This study will also investigate how many people get the most severe oral mucositis, how long it lasts, and how long it takes to occur.  The safety of GC4419 will also be assessed in this study.  To do this, the effects of GC4419 will be compared against a placebo (a substance that copies the appearance of the investigational drug but contains no active ingredient).  This study will also investigate whether GC4419 has any effect on your cancer.

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Inclusion Criteria
  • squamous cell carcinoma of the head and neck
  • treatment plan to receive IMRT delivered as single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose of 60-72 Gy
  • Treatment plan to receive standard cisplatin monotherapy
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Adequate hematologic, renal and liver function
  • Negative serum pregnancy test
  • Use of effective contraception

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Exclusion Criteria
  • Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands
  • Metastatic disease
  • Prior radiotherapy to the region of the study cancer or adjacent anatomical
  • Prior induction chemotherapy
  • Receiving any approved or investigational anti-cancer agent other than those provided for in this study
  • Concurrent participation in another interventional clinical study
  • Inability to eat soft solid food at baseline
  • Malignant tumors other than HNC within the last 5 years
  • Active infectious disease excluding oral candidiasis
  • Presence of oral mucositis at baseline
  • Known history of HIV or active hepatitis B/C
  • Female patients who are pregnant or breastfeeding
  • Known allergies or intolerance to cisplatin and similar platinum-containing compounds
  • Requirement for concurrent treatment with nitrates or other drugs that may create a risk for a precipitous decrease in blood pressure

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Merck MK-3475-412-00

Pembrolizumab or Placebo in Combination with Chemoradiation (CRT) in Subjects with Locally Advanced HNSCC (Head and Neck Squamous Cell Carcinoma)

Physician & Study Coordinator

Study Coordinator

Jillian Timer, RN, BSN
484-503-4156 

Jillian.timer@sluhn.org

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Synopsis

Treatment Agent: MK-3475

Synopsis: The purpose of this study is to evaluate and compare the safety, tolerability and anti-tumor activity of the research study drug pembrolizumab (MK-3475) in combination with chemoradiation (CRT) to placebo in combination with CRT in subjects with locally advanced head and neck squamous cell carcinoma. This is a research study to test a drug, Keytruda® (pembrolizumab) that has been approved for use in certain types of melanoma, lung cancer, and recurrent/metastatic head and neck squamous cell cancer. Keytruda® or placebo will be administered along with cisplatin and radiotherapy in this study. Cisplatin is a type of chemotherapy drug and is marketed in the United States as Platinol®.

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Inclusion Criteria
  • Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease.
  • Has provided adequate tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy
  • Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
  • Is eligible for definitive CRT and not considered for primary surgery based on investigator decision
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
  • Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

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Exclusion Criteria
  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
  • Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab
  • Has received a live vaccine within 30 days prior to the first dose of study therapy
  • Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer
  • Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study
  • Has not recovered from major surgery prior to starting study therapy
  • Has known active Hepatitis B or C
  • Has known history of Human Immunodeficiency Virus (HIV)
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has had previous allogeneic tissue/solid organ transplant
  • Has active infection requiring systemic therapy
  • Has a history of severe hypersensitivity reaction to pembrolizumab, cisplatin or radiotherapy or their analogs
  • Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy

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NRG-HN003

A Phase I and Expansion Cohort Study of Adjuvant Cisplatin, Intensity-Modulated Radiotherapy, and MK-3475 (Pembrolizumab) in High-risk Head and Neck Squamous Cell Carncinoma (HNSCC)

Physician & Study Coordinator

Study Coordinator

Jillian Timer, RN, BSN

484-503-4156

Jillian.timer@sluhn.org

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Synopsis

Treatment Agent: Cisplatin, MK-3475

Synopsis: This study tests the timing of the dose of pembrolizumab paired with the timing of the radiation and chemotherapy to see which combination is safer in people. The purpose of this study is to test the safety and schedule of adding full-dose pembrolizumab to radiation therapy and cisplatin chemotherapy. Pembrolizumab is FDA approved for treating patients with melanoma and lung cancer, and it is FDA approved for treating patients with head and neck cancer that has returned after treatment with chemotherapy (such as cisplatin). However, pembrolizumab is not part of the usual treatment of high-risk head and neck cancer, and the combination of pembrolizumab with radiation therapy and chemotherapy is investigational in this disease setting. Pembrolizumab may or may not increase the side effects of radiation therapy and chemotherapy. In this study, your doctor will carefully evaluate the side effects that you experience when pembrolizumab is added to the usual treatment.

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Inclusion Criteria

STEP 1 (REGISTRATION)

  • Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), hypopharynx or larynx
  • Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx squamous cell carcinoma (SCC) within 63 days prior to registration; Note: Patients may have a biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but demonstrate rapid gross recurrence or are determined to have gross persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
  • Patients must have at least one of the following high risk pathologic features:
    • Extracapsular nodal extension
    • Invasive cancer at the primary tumor resection margin (tumor on ink); Note: Patients who have a positive margin and undergo re-resection with final negative margin are eligible only if they can be enrolled within 63 days of initial gross total resection AND extracapsular nodal extension was also present; patients who have a positive margin and undergo re-resection with final negative margin and do not have extracapsular nodal extension, are NOT eligible
  • Pathologic stage III or IV HNSCC, including no distant metastases, based on the following minimum diagnostic workup:
    • General history/physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration
    • Examination by an ear nose and throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
    • Pre-op Imaging of the head and neck: a neck computerized tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: This imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via transfer of images and data (TRIAD); the report is to be uploaded into Rave
    • Chest imaging with either a CT scan (with or without contrast) or CT/PET (with or without contrast) that includes the chest within 120 days prior to registration ; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
  • For patients with oropharyngeal cancer only: the institution will do p16 testing, and if p16 is negative, this tissue must be submitted for central review for confirmation before Step 2 registration Note: If the institution finds that the patient is p16 positive, the patient is excluded from this trial on the basis of distinct biology, prognosis, and low- or intermediate-risk rather than high-risk status
  • Zubrod performance status of 0-1 within 28 days prior to registration
  • Absolute neutrophil count (ANC): >= 1,500 /mm^3
  • Platelets: >= 100,000 / mm^3
  • Hemoglobin: >= 8.0 g/dL (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Serum creatinine =< the institutional upper limit of normal (ULN) OR
  • Creatinine clearance (CrCl) >= 50 ml/min within 14 days prior to registration as determined by 24-hour collection or estimated by Cockraft-Gault formula
  • Serum total bilirubin: =< 1.5 X ULN OR
  • Direct bilirubin: =< ULN for patients with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN
  • International normalized ratio (INR) or prothrombin time (PT): =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated Partial Thromboplastin Time (aPTT): =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chlorine (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at the investigator's discretion
  • For women of childbearing potential, a negative serum pregnancy test within 14 days of registration
  • Female patients of childbearing potential and men receiving pembrolizumab who are sexually active with women of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of pembrolizumab Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
  • Patients with feeding tubes are eligible for the study
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry, including consent for mandatory tumor tissue, serum, and blood submission for immune correlatives (all patients) and p16 analysis (oropharyngeal cases only)

STEP 2 (REGISTRATION)

  • For patients with oropharyngeal cancer only: p16 negative, confirmed by central pathology review

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Exclusion Criteria
  • Definitive clinical or radiologic evidence of metastatic disease
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix) are permitted even if diagnosed and treated < 3 years ago
  • Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma, who are eligible
  • Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer; Note: Prior cytotoxic chemotherapy or biologic/targeted therapy for a different cancer is allowable; however, a prior anti-programmed cell death (PD)-1, anti-PD-L1, or anti-programmed cell death 1 ligand 2 (PD-L2) agent is not permitted
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity defined as follows:
    • Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration
    • Transmural myocardial infarction within 6 months prior to registration
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Note: If the infection resolves and the patient is on oral (p.o.) and still within, the required registration timeframe, then the patient is eligible
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration
    • Known history of, or any evidence of active, non-infectious pneumonitis
    • Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the cisplatin and IMRT involved in this protocol may be significantly immunosuppressive
    • A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of t pembrolizumab
    • Known history of active TB (bacillus tuberculosis)
    • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis c virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); Note: Patients who have been curatively treated for hepatitis C and have no detectable viral load are eligible
    • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Grade 3-4 electrolyte abnormalities (CTCAE, v. 4):
  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14mmol/L)
  • Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
  • Patients who are pregnant, nursing, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of pembrolizumab
  • A known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Hypersensitivity to pembrolizumab or any of its excipients;
  • Patients who have received a live vaccine within 30 days of planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Patients for whom it is not in the best interest to participate in the study, in the opinion of the treating investigator

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