Clinical trial NCT02764593: Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer
Official title: Safety Evaluations of Nivolumab (Anti-PD-1) Added To Chemotherapy (CRT) Platforms In Patients With Intermediate And High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
Keywords: Head and Neck Squamous Cell Carcinoma
HNSCC
Nivolumab
Lead sponsor: RTOG Foundation, Inc.
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2016-05-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.
* Intermediate-risk group: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status \> 10 Pack-years, stage T1-2N2b-N3 OR ≤ 10 pack-years, stage T4N0-N3 or T1-3N3.
* High-risk group: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T1-2N2a-N3 or T3-4-N0-3 based on the following diagnostic workup:

  * Mandatory submission of H\&E and p16 stained slides for central review of p16 staining is required for oropharyngeal patients and H\&E stained slide block (or punch biopsy of paraffin block) for PD-L1 expression analysis for all patients
  * History/physical examination within 28 days prior to registration
  * Examination by Radiation Oncologist, Medical Oncologist, and Ear, Nose, Throat (ENT) or Head \& Neck Surgeon within 28 days prior to registration
  * Fiberoptic exam with laryngopharyngoscopy within 28 days prior to registration
  * Diagnostic quality, cross sectional imaging of the thorax within 28 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable.
  * Diagnostic quality CT or MRI of neck, with contrast, within 28 days prior to registration; a 18-F-FDG-PET/CT of the neck only is acceptable as a substitute if the CT is of diagnostic quality and with IV contrast.
* Age ≥ 18 years
* The trial is open to both genders

Exclusion Criteria:

* Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.
* Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist.
* Carcinoma of the neck of unknown primary site origin (even if p16-positive).
* Absence of RECIST, v. 1.1 defined measurable disease.
* Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.
* Simultaneous primary cancers or separate bilateral primary tumor sites.
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
* Prior systemic chemotherapy for the study cancer.
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
* Patients with active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.
* Use of systemic corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids.
* Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: From the first dose of nivolumab to 28 days after the completion of radiation therapy.
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Orlando
country: United States
facility: University of Florida Cancer Center at Orlando Health
state: Florida
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC - Shadyside Hospital
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: RTOG Foundation
name: Maura Gillison, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: RTOG Foundation
name: Robert Ferris, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, Jordan RC, Moore KL, Truong MT, Kirsch C, Chakravarti A, Blakaj DM, Clump DA, Ohr JP, Deeken JF, Gensheimer MF, Saba NF, Dorth JA, Rosenthal DI, Leidner RS, Kimple RJ, Machtay M, Curran WJ Jr, Torres-Saavedra P, Le QT. Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):847-860. doi: 10.1016/j.ijrobp.2022.10.008. Epub 2022 Oct 11.