Cetuximab and Nivolumab in Treating Patients with Recurrent or Metastatic Oral Cavity, Oropharyngeal, Paranasal Sinus, Hypopharyngeal, or Laryngeal Cancer

Status: Active

Description

This phase I / II trial studies the side effects and how well cetuximab and nivolumab work in treating patients with oral cavity, oropharyngeal, paranasal sinus, hypopharyngeal, or laryngeal cancer that have come back or spread to other places in the body. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Some tumors need growth factors, which are made by the body's white blood cells, to keep growing. Growth factor inhibitors, such as cetuximab may interfere with the growth factor and stop the tumor from growing.

Eligibility Criteria

Inclusion Criteria

  • Patients 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
  • COHORT A: Patients 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)
  • COHORT A: Patients with persistent disease following radiation therapy administered with a chemotherapy sensitizer may also be included
  • COHORT A: Patients 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 (recurs within 6 months of last dose of chemotherapy given as a sensitizer to definitive radiation) may enroll in this study as a first-line therapy
  • COHORT A: Prior treatment with a combination of cetuximab and a PD-1/PD-L1 inhibitor is excluded. Prior treatment with cetuximab or a PD-1/PD-L1 inhibitor is allowed as long as not previously given in combination
  • COHORT B: Patients must have recurrent or metastatic HNSCC that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
  • COHORT B: Patients with persistent disease following radiation therapy administered with a chemotherapy sensitizer may NOT be included
  • COHORT B: Patient must NOT have any systemic therapy for recurrent and/or metastatic disease 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).
  • COHORT B: Prior systemic therapy if given as neoadjuvant, concurrently with radiation and/or adjuvant setting must have been completed > 6 months prior to enrollment
  • COHORT B: There is no evidence of disease progression for at least 6 months after completion of prior systemic therapy
  • COHORT B: Patients that refuse potentially curative salvage surgery for recurrent disease are ineligible
  • COHORT B: Prior treatment with a combination of cetuximab and a PD-1/PD-L1 inhibitor is NOT included
  • COHORT B: Prior treatment with a PD-1/PD-L1 inhibitor is NOT included
  • COHORT B: Prior treatment with cetuximab or EGFR inhibitors given concurrently with radiation as a radiation sensitizer is included. However, cetuximab or EGFR inhibitors given in the recurrent and/or metastatic setting is NOT included
  • Patients 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 Response Evaluation Criteria in Solid Tumors (RECIS)T version 1.1
  • Life expectancy of greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count > 1,500/uL
  • Hemoglobin > 9 g/dL
  • Platelets > 100,000/uL
  • Total bilirubin =< 1.5 mg/dL X institutional upper limits of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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)
  • If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods)
  • Female patients 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

  • Patients who experienced grade 3 or above skin toxicity from prior EGFR inhibiting therapy
  • Patients who have experienced grade 3 or above toxicity from prior anti-PD1 therapy
  • Patients who have p16 negative squamous cell carcinoma of unknown primary in cervical lymph node
  • Patients with primary nasopharynx or salivary gland cancers are excluded
  • 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
  • Patients who had undergone any major surgery within 4 weeks of study enrollment
  • Patients who had undergone any palliative radiation within 2 weeks of study enrollment
  • Patients who have had other investigational agents within 4 weeks or 5 half-lives, whichever is shorter, of the study enrollment
  • Patients who 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
  • Subjects with 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
  • The patient has 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
  • The patient has uncontrolled or poorly controlled hypertension (> 180 mmHg systolic or > 130 mmHg diastolic) at the time of enrollment
  • The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab and/or nivolumab
  • The patient is pregnant or breast-feeding
  • Patients with known active human immunodeficiency virus (HIV), hepatitis (Hep) B, or Hep C infection will be excluded; if not clinically indicated, the patients do not need to be tested

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Christine H. Chung
Phone: 813-745-5431
Email: Christine.Chung@Moffitt.Org

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Nabil F. Saba
Phone: 404-778-3126
Email: nfsaba@emory.edu

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Contact: Marcelo Raul Bonomi
Phone: 614-293-0463
Email: Marcelo.Bonomi@osumc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of concurrent cetuximab and nivolumab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). (Phase I)

II. To determine the 1-year overall survival rate of concurrent cetuximab and nivolumab in patients who had progressed on at least one prior line of treatment for their recurrent and/or metastatic HNSCC. (Phase II Cohort A)

III. To determine the 1-year overall survival rate of concurrent cetuximab and nivolumab in patients who has not had any prior treatments for their recurrent and/or metastatic HNSCC. (Phase II Cohort B)

SECONDARY OBJECTIVES:

I. To estimate response rate of patients treated with concurrent cetuximab and nivolumab who have recurrent and/or metastatic HNSCC. (Phase II)

II. To estimate progression-free survival of patients treated with concurrent cetuximab and nivolumab who have recurrent and/or metastatic HNSCC. (Phase II)

III. To evaluate the toxicity of the cetuximab and nivolumab combination in this patient population. (Phase II)

EXPLORATORY OBJECTIVES:

I. To identify potential biomarkers related to response to concurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC.

OUTLINE:

Patients receive cetuximab intravenously (IV) and nivolumab IV on day 1 of cycle 1 and every 2 weeks of subsequent courses. Treatment repeats every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Moffitt Cancer Center

Principal Investigator
Christine H. Chung

Trial IDs

Primary ID MCC-19178
Secondary IDs NCI-2017-02373
Clinicaltrials.gov ID NCT03370276