## Protocol Section
### Identification Module
**NCT ID:** NCT03878979

**Brief Title:** Preoperative Immune Checkpoint Inhibitor for Patients With Primary Untreated or Recurrent/Metastatic SCCHN

**Official Title:** Preoperative Immune Checkpoint Inhibitor Therapy for Patients With Primary Untreated or Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (RM-SCCHN)

#### Organization Study ID Info
**ID:** J1923
#### Organization
**Class:** OTHER
**Full Name:** Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
#### Secondary ID Infos
**Domain:** JHM IRB
**ID:** IRB00207577
**Type:** OTHER
**Domain:** Bristol-Myers Squibb
**ID:** CA209-9H7
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2023-10-17

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-02-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-02-15

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-10-17

**Type:** ACTUAL

#### Start Date
**Date:** 2019-07-08

**Type:** ACTUAL

**Status Verified Date:** 2024-02

#### Study First Post Date
**Date:** 2019-03-18
**Type:** ACTUAL
**Study First Submit Date:** 2019-03-15
**Study First Submit QC Date:** 2019-03-15
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Bristol-Myers Squibb

#### Lead Sponsor

**Class:** OTHER

**Name:** Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or recurrent squamous cell carcinoma of head and neck (SCCHN).

**Detailed Description:** This research is being done to see if it is safe and feasible to give the investigational drugs, nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or recurrent squamous cell carcinoma of head and neck (SCCHN). Patients with recurrent disease may have a limited number of sites of metastatic (spread) squamous cell carcinoma of head and neck. Another goal of this study is to learn how nivolumab impacts the immune system's ability to treat the cancer. While nivolumab is approved by the U. S. Food and Drug Administration (FDA) for the treatment of patients with metastatic SCCHN with progression on or after platinum-based chemotherapy, the word "investigational" in this context means that the study drugs are not approved by the FDA for the treatment of head and neck cancers prior to surgery and thus is still being tested in research studies. However, the FDA is allowing the use of nivolumab in this study.

This study will have two arms. Cohort (arm) 1 will examine one dose of nivolumab given about 4 weeks before surgical resection (removal) of a newly diagnosed SCCHN. Twelve patients will be enrolled to this arm. Cohort 2 will examine one dose of nivolumab given about 4 weeks before surgical resection (removal) of SCCHN which has recurred and possibly spread to distant sites, but still can be resected with one surgery. Twelve patients will be enrolled to this arm.

### Conditions Module

**Conditions:**

- Head and Neck Squamous Cell Carcinoma

- Head and Neck Cancer

- Head and Neck Cancer Metastatic

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** The study will accrue to 2 cohorts, each of which consists of about 12 patients. If enrollment on 1 cohort is significantly faster, the lesser enrolling cohort number of patients may be decreased in favor of the better enrolling cohort to keep the total number of evaluable patients at 24 patients.Total of 24 patients will be accrued to the study.

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 26

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** One dose of nivolumab given about 4 weeks before surgical resection (removal) of a newly diagnosed SCCHN.

**Intervention Names:**

- Drug: Nivolumab 480mg and surgical resection

**Label:** Newly diagnosed SCCHN

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** One dose of nivolumab given about 4 weeks before surgical resection (removal) of SCCHN which has recurred.

**Intervention Names:**

- Drug: Nivolumab 480mg and surgical resection

**Label:** Reccurence of SCCHN

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Newly diagnosed SCCHN

- Reccurence of SCCHN

**Description:** One dose of Nivolumab 480mg given four weeks prior to surgical resection.

**Name:** Nivolumab 480mg and surgical resection

**Other Names:**

- Opdivo

- ONO-4538

- BMS-936558

- MDX 1106

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Safety of neoadjuvant nivolumab administration in patients with newly diagnosed head and neck cancer and those with locoregional recurrence or oligometastatic disease undergoing surgical resection measured by number of participants with drug related adverse events as defined by CTCAE v5.0, occurring up to 100 days after the last dose of nivolumab or 30 days after surgery (whichever is longer)

**Measure:** Safety as measured by number of participants with drug-related adverse events

**Time Frame:** Up to 100 days after the last dose of nivolumab or 30 days after surgery (whichever is longer)

**Description:** Feasibility of neoadjuvant nivolumab administration in patients with newly diagnosed head and neck cancer and those with locoregional recurrence or oligometastatic disease undergoing surgical resection, measured by number of participants with successful completion of preoperative treatment and proceeding to surgery without any extended treatment related delays more than \> 28 days from pre-planned day 0.

**Measure:** Feasibility as measured by number of participants with successful completion of preoperative treatment and no extended treatment-related delays

**Time Frame:** Up to 100 days after the last dose of nivolumab or 30 days after surgery (whichever is longer)

#### Secondary Outcomes

**Description:** Number of participants with \< 10% residual tumor in the resection specimen.

**Measure:** Major pathologic response rate

**Time Frame:** Day 0 (after surgery)

**Description:** Number of months until radiologic or clinical progression or death, whichever occurs first.

**Measure:** Progression free survival (PFS)

**Time Frame:** up to 3 years

**Description:** Number of participants with response as determined by RECIST version 1.1 and immune-related response criteria (irRC). Per RECIST criteria, Complete response (CR) is a disappearance of all target lesions, Partial response (PR) is \>= 30% decrease in the sum of the largest diameter (LD) of target lesions, Progressive disease (PD) is \>= 20% increase in the sum of the LD of target lesions.

Per irRC, immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is a 50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a 25% increase in tumour burden from the lowest level recorded.

**Measure:** Radiographic response rate

**Time Frame:** up to 4 weeks post-intervention

### Eligibility Module

**Eligibility Criteria:** Inclusion:

Cohort 1: Subjects must have histologically confirmed previously untreated squamous cell carcinoma of the head and neck which is amenable to surgical resection as part of standard of care.

Cohort 2: Subjects must have histologically confirmed recurrent squamous cell carcinoma of head and neck, which is amenable for salvage surgery. Sites of recurrence may either be locoregional or distant if resection can be done ideally in one surgical field.

* The primary site should be a head and neck squamous cell carcinoma (including, but not limited to oral cavity, oropharynx, hypopharynx, or larynx, paranasal sinuses, nasal cavity). Squamous cell carcinoma of unknown primary, diagnosed in lymph nodes in neck, can be included but should be tested for p16 and confirmed specific assay.
* Subjects with oropharyngeal primary tumors must have confirmation of human papillomavirus (HPV) tumor status per clinical standards, although not necessary at enrollment.
* Subjects must have been determined to be candidates for surgical resection by a multidisciplinary team including a surgeon, a medical oncologist and a radiation oncologist.
* Subjects must have at least one lesion that can be biopsied at baseline.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
* Age \>18 years.
* Life expectancy of greater than 6 months.
* Patients must have normal organ and marrow function as defined below:

  * leukocytes ≥ 1,500/ microliter (mcL)
  * absolute neutrophil count ≥ 1,000/mcL
  * platelets ≥ 100,000/mcL
  * total bilirubin ≤ 1.5 X institutional upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL)
  * AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal
  * Creatinine OR creatinine clearance within normal institutional limits OR ≥ 40 mL/min (using modified Cockcroft-Gault formula) for patients with creatinine levels above institutional normal.
* Resting and walking O2 saturation must remain above 90% at the time of screening
* Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
* Women must not be breastfeeding
* Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment and for 5 months post-treatment completion. Women should use an adequate method(s) of contraception (Refer to nivolumab IB for WOCBP and methods of contraception to be provided)
* Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (Refer to protocol appendix E) for the duration of treatment with study treatment(s) and 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception
* Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report adverse events (AEs), understand the drug dosing schedule and use of medications to control AEs.
* Measurable disease - either radiologically (per RECIST) or clinically measurable on exam in order to assess treatment response.

Exclusion Criteria

* Any active history of a known autoimmune disease. Subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Patients who have had prior chemotherapy for newly diagnosed (cohort 1) or recurrent (cohort 2) head and neck cancer. In cohort 2 only, previous perioperative chemotherapy or chemoradiation for the management of localized or locally advanced disease permitted.
* Patients who had prior surgical resection of distant metastasis (metastatectomy) within 3 months of enrollment.
* Patients who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti CD137, anti-CTLA-4 antibody therapies, any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Any live / attenuated vaccine (eg varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella (MMR)) during treatment and until 100 days post last dose.
* Patients with uncontrolled brain metastases
* Patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks without the use of steroids or on stable or decreasing dose of \< 10mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of carcinomatous meningitis are not eligible.
* Patients who have an active concurrent malignancy that is not controlled/cured and could impact life expectancy within the next 3 years. E.g. patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma or treated prostate cancer with no evidence of disease progression may be allowed to enroll after review by the study team.
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, administration of live vaccination in the prior 3 months, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction or new onset angina within six months of enrollment, or psychiatric illness/social situations that would limit compliance with study requirements.
* Women who are pregnant or nursing.
* Men with female partners who are not willing to use contraception.
* Active infection with hepatitis B or hepatitis C.
* Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids and adrenal replacement steroid doses \< 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
* Patients Epstein-Barr virus + (EBV+) with nasopharynx carcinoma
* Patient with HIV are excluded given the unknown risk of interaction with HAART and the unknown benefit of immunotherapy in this population.
* Participants who have received a live / attenuated vaccine within 30 days of first treatment.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Baltimore

**Country:** United States

**Facility:** Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

**State:** Maryland

**Zip:** 21287

#### Overall Officials

**Official 1:**

**Affiliation:** Johns Hopkins University

**Name:** Tanguy Lim-Seiwert, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000018307

- Term: Neoplasms, Squamous Cell

- ID: D000009371

- Term: Neoplasms by Site

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M9348

- Name: Head and Neck Neoplasms

- Relevance: HIGH

- As Found: Head and Neck Cancer

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M5550

- Name: Carcinoma, Squamous Cell

- Relevance: HIGH

- As Found: Squamous Cell Carcinoma

- ID: M1689

- Name: Squamous Cell Carcinoma of Head and Neck

- Relevance: HIGH

- As Found: Head and Neck Squamous Cell Carcinoma

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M20451

- Name: Neoplasms, Squamous Cell

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000002294

- Term: Carcinoma, Squamous Cell

- ID: D000006258

- Term: Head and Neck Neoplasms

- ID: D000077195

- Term: Squamous Cell Carcinoma of Head and Neck

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000082082

- Term: Immune Checkpoint Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1854

- Name: Nivolumab

- Relevance: HIGH

- As Found: Prospective

- ID: M2342

- Name: Immune Checkpoint Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077594

- Term: Nivolumab

### Misc Info Module

- Version Holder: 2024-05-24
