Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer

Head and Neck Squamous Cell Carcinoma (HNSCC) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02764593
• Other study ID #: RTOG 3504
• Secondary ID: RF 3504CA209-410
• Status: Completed
• Phase: Phase 1
• Start date: June 2016
• Est. completion date: February 21, 2022

Study information

• Verified date: November 2022
• Source: RTOG Foundation, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 21, 2022
• Est. primary completion date: September 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Nivolumab
Anti-PD-1 targeted immunotherapy
• Cisplatin
Anti-cancer alkylating agent
• Cetuximab
Epidermal Growth Factor Receptor (EGFR) antagonist

Radiation:
• IMRT
High-precision radiotherapy

Locations

Country	Name	City	State
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	University of Florida Cancer Center at Orlando Health	Orlando	Florida
United States	Stanford Cancer Institute	Palo Alto	California
United States	UPMC - Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
RTOG Foundation, Inc.	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT)	A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows: 1) Any = grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of > 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (= 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab.	From the first dose of nivolumab to 28 days after the completion of radiation therapy.