Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in SCCHN

Study Overview
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Brief Summary
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This research study is studying a combination of two immunotherapy drugs, as a possible treatment for locoregionally recurrent squamous cell carcinoma of the head and neck. The immunotherapy drugs involved in this study are: Nivolumab (Opdivo™) Lirilumab

Detailed Description
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This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or combination of drugs to learn whether it works in treating a specific disease. Investigational means that the drug/s is being studied. The purpose of this study is to evaluate effectiveness (how well the drug/s work) of nivolumab in combination with lirilumab in participants with SCCHN. Nivolumab and lirilumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells. Both nivolumab and lirilumab have been demonstrated to activate the immune system to attack cancer cells in participants with different types of cancers. In November, 2016, the Food and Drug Administration (FDA) approved nivolumab for the treatment of participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Lirilumab is not FDA approved as of now.

Official Title
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Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in Patients With Relapsed, Resectable Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Lirilumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have histologically or cytologically confirmed locoregionally recurrent squamous cell carcinoma of the head and neck (including any primary site, such as oral cavity, oropharynx, larynx or hypopharynx, and nasopharyngeal carcinoma) Must be a candidate for salvage surgery Willing to provide blood and tissue from diagnostic biopsy and at the time of surgery Has documented disease-free interval (DFI) > 8 weeks after completion of initial therapy; DFI is from the time of completion of initial treatment to the diagnosis of local or locoregional recurrence Any HPV status or smoking history is permitted. Oropharyngeal cancer patients are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV PCR or ISH testing Age 18 years or older ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A) Participant must have normal organ and marrow function as defined below within 21 days prior to study registration: leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin ≤2.0 g/dL AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal Ability to understand and the willingness to sign a written informed consent document Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of contraception. WOCBP should plan to use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours prior to the start of nivolumab Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL Men who are sexually active with WOCBP must agree to use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception Exclusion Criteria: Existing significant autoimmune conditions. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded. Patients cannot be on long-term (> 4 weeks) corticosteroids at doses exceeding prednisone 20 mg (or its equivalent) prior to enrollment. Short-term corticosteroid dosing is permitted as long as steroids are discontinued within 2 weeks of study enrollment. Subject who has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Subject who has been treated with immunotherapy. This includes prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Subject with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, baseline brain imaging is not required prior to enrollment in the study if patients are asymptomatic. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, eg, Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative). Known non-infectious pneumonitis or any history of interstitial lung disease. Receipt of a live vaccine within 30 days of start of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab+Lirilumab<br>The drugs will be administered intravenously. A single dose of Nivolumab and Lirilumab will be administered prior Salvage surgical resection. In Cycle 1-3: Nivolumab will be administered on Days 1 and 15 and lirilumab will be administered on Day 1 of each 28 day long cycle In Cycle 4-6 and beyond: Nivolumab and lirilumab will be administered on Day 1 of each 28 day long cycle. | Drug: Nivolumab<br>* Nivolumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells<br>Drug: Lirilumab<br>* Lirilumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-Year Disease-Free Survival Percentage | The percentage of patients who were alive and disease free at one year past salvage surgery. Patients who were alive at last contact prior to the one year mark are censored. Data analysis conducted through Kaplan Meier methods. | 1 year since salvage surgery, up to 1 year and 23 days since treatment start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response at Time of Salvage Surgery | Response is classified using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Complete Response - Disappearance of all lesions and pathologic lymph nodes. Partial Response - At least 30% decrease in sum of longest diameters (SLD) for the target lesions, no new lesions, and no progression of non-target lesions. Progressive Disease - At least 20% increase in SLD compared to smallest SLD in study or progression of non-target lesions or development of new lesions Stable Disease - No Partial Response and no Progressive Disease. | At the time of salvage surgery, up to 23 days from treatment start date. | 
| Median Disease-Free Survival Rate | The median time that patients were alive and disease free after salvage surgery. Patients who were alive at last contact are censored at last contact. Data analysis conducted through Kaplan Meier methods | Up to 27.2 months post salvage surgery, up to 28 months total. | 
| 1-Year Overall Survival Percentage | Percentage of participants who were alive at 1 year since salvage surgery. Patients alive at last contact prior to 1 year were censored. | 1 year post salvage surgery, up to 1 year and 23 days post treatment start. | 
| Median Change in Programmed Cell Death Ligand - 1 Combined Positive Score | The median change in Programmed Cell Death Ligand - 1 Combined Positive Score (PD-L1 CPS) from baseline to surgery. The score is derived from tumor tissue samples that measures the presence of both tumor and immune cell staining for the PD-L1 marker. Scored from 0-100, a higher score suggests the patient might respond better to treatment. A pathological responder is defined as having less than 50% viable tumor at the time of surgery. | Measured at baseline and then at time of salvage surgery, up to 23 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Carcinoma