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

NCT ID: NCT03370276

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-20
• Study Completion Date: 2025-12-31

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.

Detailed Description

PHASE I: Participants will be enrolled sequentially and treated at Dose Level 1, or Dose Level -1, every 2 weeks for 12 cycles or until discontinuation.

Each cycle is 4 weeks. Cetuximab is given alone in lead-in period at Day -14 before Cycle 1 only. In all subsequent doses starting Cycle 1 Day 1, nivolumab and cetuximab will be given concurrently. Dose limiting toxicity (DLT) assessment will be performed during Cycle 1 and will start with the initiation of the combination of cetuximab and nivolumab (4 weeks).

PHASE II: Once the maximum tolerated dose (MTD) or the recommended phase II dose of cetuximab is determined in Phase I, accrual to the phase II will begin.

FOLLOW-UP: Participants will be followed for 2 years from End of Treatment. The imaging studies will be performed every 8 weeks (2 cycles) of the treatments during Cycle 1-6 and then every 12 weeks during Cycle 7-12 as per standard of care. Patient will be followed by treating physicians as per standard of care.

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; Squamous Cell Cancer; Head and Neck Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I - Moffitt Site Only

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Cetuximab

Intervention Type: DRUG

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

Phase II - Affiliate Sites Only

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Cetuximab

Intervention Type: DRUG

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

Phase II - Moffitt Site Only

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Cetuximab

Intervention Type: DRUG

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

Phase I - Affiliate Sites Only

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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

Cetuximab

Intervention Type: DRUG

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

Interventions

Nivolumab

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

Intervention Type: DRUG

Cetuximab

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

Intervention Type: DRUG

Other Intervention Names

Opdivo; Erbitux

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Pregnant or breast-feeding.
• Known active HIV, Hep B, or Hep C infection. If not clinically indicated, the patients do not need to be tested.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

James and Esther King Biomedical Research Program

OTHER

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine H. Chung, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

The Ohio State University

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35676062 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://moffitt.org/clinical-trials-research/

Moffitt Cancer Center Clinical Trials website

Other Identifiers

MCC-19178

Identifier Type: -

Identifier Source: org_study_id