Preoperative Immune Checkpoint Inhibitor for Patients With Primary Untreated or Recurrent/Metastatic SCCHN

NCT03878979 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J1923IRB00207577CA209-9H7
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Nivolumab, also known as (Bristol Myers Squibb (BMS)) BMS-936558, before surgery to people with newly diagnosed or recurrent squamous cell carcinoma of head and neck (SCCHN).

Conditions

Head and Neck Squamous Cell Carcinoma; Head and Neck Cancer; Head and Neck Cancer Metastatic

Outcome Measures

Primary Outcomes (2)

• Safety as Measured by Number of Participants With Drug-related Adverse Events

  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)

  Up to 100 days after the last dose of nivolumab or 30 days after surgery, whichever is longer (up to 100 days per participant)

• Feasibility as Measured by Number of Participants With Successful Completion of Preoperative Treatment and no Extended Treatment-related Delays

  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.

  Up to 100 days after the last dose of nivolumab or 30 days after surgery (whichever is longer per participant)

Secondary Outcomes (3)

• Major Pathologic Response Rate

  Day 0 (Surgery)

• Progression Free Survival (PFS)

  up to 3 years

• Radiographic Response Rate

  up to 4 weeks after the last dose of nivolumab

Study Arms (2)

Newly diagnosed SCCHN

EXPERIMENTAL

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

Drug: Nivolumab 480mg and surgical resection

Recurrence of SCCHN

EXPERIMENTAL

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

Drug: Nivolumab 480mg and surgical resection

Interventions

Nivolumab 480mg and surgical resection DRUG

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

Also known as: Opdivo, Ono Pharmaceutical (ONO) 4538, BMS-936558, Medarex Incorporated (MDX) 1106

Newly diagnosed SCCHN; Recurrence of SCCHN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT) (SGPT) ≤ 3 X institutional upper limit of normal

You may not qualify if:

• 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 (metastasectomy) within 3 months of enrollment.
• Patients who received prior therapy with anti-programmed death (PD) 1 (anti-PD-1), anti-PD-L1, anti-PD-L2, cluster of differentiation (CD)137 (CD137), anti-cytotoxic T-lymphocyte associated (CTLA) protein 4 (anti-CTLA-4) (cytotoxic T-lymphocyte associated protein 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

Nivolumab; MD1

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Tanguy Seiwert
• Organization: Johns Hopkins University

tseiwert@jhmi.edu

443-287-8312

Study Officials

• Tanguy Lim-Seiwert, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 18, 2019
• Study Start: July 8, 2019
• Primary Completion: October 17, 2023
• Study Completion: October 17, 2023
• Last Updated: November 21, 2024
• Results First Posted: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)