Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

NCT03370276 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MCC-19178
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to find out if the combination of two established anti-cancer therapies are beneficial in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Specifically, investigators want to determine if the combination of Cetuximab and nivolumab can help people with advanced cases of HNSCC. Both cetuximab and nivolumab have been used separately to treat HNSCC and are Food and Drug Administration (FDA) approved in this type of cancer.

Conditions

Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Head and Neck Carcinoma; Squamous Cell Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose

  Maximum Tolerated Dose (MTD).. The target Dose Limiting Toxicity (DLT) rate is \<25%. The MTD will be defined as the dose of cetuximab and nivolumab in which \<1 of 3 patients experience a DLT or \<2 of 6 patients experience a DLT with the next higher dose having at least 2 patients experiencing a DLT. The MTD is the highest dose at which at most 1 of 6 patients has a DLT. This study will utilize the Cancer Therapy Evaluation Program CTCAE version 4.1 for toxicity and event reporting. Dose-limiting toxicities will be observed until patients have completed Cycle 1 (4 weeks).

  Up to 12 months

• Phase II: Overall Survival (OS)

  One year overall survival of concurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC. OS: The length of time from the start of treatment until death by any cause.

  Up to 24 months

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  Up to 48 months

• Progression Free Survival (PFS)

  at 12 months

• Number of Study Treatment Related Adverse Events

  Up to 48 months

Study Arms (4)

Phase I - Affiliate Sites Only

EXPERIMENTAL

Nivolumab and dose escalation of Cetuximab. Dose Level 1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Dose Level -1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m\^2; Nivolumab 240 mg.

Drug: Nivolumab; Drug: Cetuximab

Phase I - Moffitt Site Only

EXPERIMENTAL

Nivolumab and dose escalation of Cetuximab. Dose Level 1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Dose Level -1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m\^2; Nivolumab 240 mg.

Drug: Nivolumab; Drug: Cetuximab

Phase II - Affiliate Sites Only

EXPERIMENTAL

Nivolumab and Cetuximab at recommended Phase II dose (RP2D).

Drug: Nivolumab; Drug: Cetuximab

Phase II - Moffitt Site Only

EXPERIMENTAL

Nivolumab and Cetuximab at recommended Phase II dose (RP2D).

Drug: Nivolumab; Drug: Cetuximab

Interventions

Nivolumab DRUG

Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.

Also known as: Opdivo

Phase I - Affiliate Sites Only; Phase I - Moffitt Site Only; Phase II - Affiliate Sites Only; Phase II - Moffitt Site Only

Cetuximab DRUG

Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.

Also known as: Erbitux

Phase I - Affiliate Sites Only; Phase I - Moffitt Site Only; Phase II - Affiliate Sites Only; Phase II - Moffitt Site Only

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, nasal cavity, hypopharynx, or larynx. Squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive.
• Must have recurrent or metastatic HNSCC stage III/IV that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).Patients with persistent disease following radiation therapy administered with a chemotherapy sensitizer may also be included.
• Must have progressed on at least one prior line of chemotherapy, targeted therapy, palliative radiation, and/or biological therapy regimen for their recurrent and/or metastatic HNSCC. However, if patients are likely to be intolerant to standard first-line systemic chemotherapy, the patients are eligible to enroll to this study as the first-line therapy. Additionally, patients with persistent disease or platinum-refractory recurrent disease may enroll in this study as a first-line therapy.
• Must NOT have any systemic therapy for recurrent and/or metastatic disease except if given as a part of a multimodality treatment (i.e. re-irradiation and systemic therapy for curable intent of locally recurrent disease).
• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in RECIST version 1.1.
• Must be ≥ 18 years of age.
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Must have normal organ function: Absolute neutrophil count \> 1,500/μL; Hemoglobin \> 9 g/dL; Platelets \> 100,000/μL; Total bilirubin ≤ 1.5 mg/dL X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) \< 3 X institutional ULN (or 5.0 X the ULN in the setting of liver metastasis); Serum creatinine of ≤ 1.5 X ULN or creatinine clearance \> 40 mL/minute (using Cockcroft/Gault formula): Female creatinine clearance = (140 - age in years) x weight in kg x 0.8572 x serum creatinine in mg/ dL; Male creatinine clearance = (140 - age in years) x weight in kg x 1.0072 x serum creatinine in mg/dL.
• Participants, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Have experienced grade 3 or above skin toxicity from prior Epidermal growth factor receptor (EGFR) inhibiting therapy.
• Have experienced grade 3 or above toxicity from prior anti-PD1 therapy.
• Have p16 negative squamous cell carcinoma of unknown primary in cervical lymph node.
• Patients with primary nasopharynx or salivary gland cancers.
• Patients who have had chemotherapy, biological therapy or definitive radiation within 4 weeks of the study enrollment or those who have not recovered from adverse events to ≤ Grade 1 due to agents administered more than 4 weeks earlier.
• Had undergone any major surgery within 4 weeks of study enrollment.
• Had undergone any palliative radiation within 2 weeks of study enrollment.
• Have had other investigational agents within 4 weeks or 5 half-lives, whichever is shorter, of the study enrollment.
• Have known leptomeningeal metastases or untreated or symptomatic brain metastases. Treated, asymptomatic brain metastasis can be included.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease requiring systemic steroids, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Have clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
• Have uncontrolled or poorly controlled hypertension (\>180 mmHg systolic or \> 130 mmHg diastolic) at the time of enrollment.
• Prior treatment with a combination of cetuximab and a PD-1/PD-L1 inhibitor. Prior treatment with cetuximab or a PD-1/PD-L1 inhibitor is allowed as long as not previously given in combination.
• A history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab and/or nivolumab.

Sponsors & Collaborators

• Bristol-Myers Squibb: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead
• James and Esther King Biomedical Research Program: collaborator
• Eli Lilly and Company: collaborator

Study Sites (3)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Wang X, Muzaffar J, Kirtane K, Song F, Johnson M, Schell MJ, Li J, Yoder SJ, Conejo-Garcia JR, Guevara-Patino JA, Bonomi M, Bhateja P, Rocco JW, Steuer CE, Saba NF, Chung CH. T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma. J Immunother Cancer. 2022 Jun;10(6):e004512. doi: 10.1136/jitc-2022-004512.

  PMID: 35676062 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

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

Interventions

Nivolumab; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck 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: Christine Chung, MD
• Organization: Moffitt Cancer Center

Christine.Chung@moffitt.org

813-745-5061

Study Officials

• Christine H. Chung, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 12, 2017
• Study Start: December 20, 2017
• Primary Completion: September 4, 2021
• Study Completion: December 23, 2023
• Last Updated: April 2, 2026
• Results First Posted: December 20, 2022

Record last verified: 2026-03

Locations

US (3)