Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Purpose
This phase III trial compares the effect of adding cetuximab to pembrolizumab versus pembrolizumab alone in treating patients with head and neck squamous cell carcinoma (HNSCC) that has come back after a period of improvement (recurrent) and/or that has spread from where it first started (primary site) to other places in the body (metastatic). Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving cetuximab and pembrolizumab together may be more effective at treating patients with recurrent and/or metastatic HNSCC than pembrolizumab alone.
Conditions
- Metastatic Head and Neck Squamous Cell Carcinoma
- Metastatic Hypopharyngeal Squamous Cell Carcinoma
- Metastatic Laryngeal Squamous Cell Carcinoma
- Metastatic Oral Cavity Squamous Cell Carcinoma
- Metastatic Oropharyngeal Squamous Cell Carcinoma
- Recurrent Head and Neck Squamous Cell Carcinoma
- Recurrent Hypopharyngeal Squamous Cell Carcinoma
- Recurrent Laryngeal Squamous Cell Carcinoma
- Recurrent Neck Squamous Cell Carcinoma of Unknown Primary
- Recurrent Oral Cavity Squamous Cell Carcinoma
- Recurrent Oropharyngeal Squamous Cell Carcinoma
- Refractory Head and Neck Squamous Cell Carcinoma
- Refractory Hypopharyngeal Squamous Cell Carcinoma
- Refractory Laryngeal Squamous Cell Carcinoma
- Refractory Oral Cavity Squamous Cell Carcinoma
- Refractory Oropharyngeal Squamous Cell Carcinoma
- Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
- Stage IV Hypopharyngeal Carcinoma AJCC v8
- Stage IV Laryngeal Cancer AJCC v8
- Stage IV Lip and Oral Cavity Cancer AJCC v8
- Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis head and neck squamous cell carcinomas (HNSCC).
- Previously untreated for recurrent and/or metastatic disease incurable by local
therapies.
- Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx.
- Note: Other primary tumor sites of HNSCC, including nasopharynx primary tumor
are not eligible. Unknown primary tumors may be eligible and can be enrolled at
the discretion of the treatment team with approval by the study chair.
- Measurable disease.
- Must have platinum-refractory disease defined as disease progression during or ≤ 6
months after completion of definitive therapy (chemoradiation therapy) or adjuvant
(post-operative) therapy.
- Patient must have a combined positive score PD-L1 positive (CPS >/= 1) tumor.
- Any radiation therapy must be completed >= 10 days prior to registration.
- Patients should not have received any prior treatment in the recurrent or metastatic
setting.
- Prior therapy with anti PD-1/PD-L1 monoclonal antibody or cetuximab in the curative
setting is allowed if last treatment dose was >= 6 months prior to registration
without evidence of disease progression during that treatment period.
- Patient has not received a live vaccine within 30 days prior to registration.
- Patient does not have a history of any contraindication or has a severe
hypersensitivity to any component of pembrolizumab or cetuximab (≥ grade 3).
- Patient has not received chronic systemic steroid therapy (in dosing exceeding 10 mg
daily of prednisone or equivalent) or any other form of immunosuppressive therapy
within 7 days prior to registration.
- Patient with oropharyngeal cancer only must have negative results from testing of
human papillomavirus (HPV) status defined as p16 immunohistochemistry (IHC) and/or
HPV in situ hybridization (ISH).
- Note: A Clinical Laboratory Improvement Act (CLIA) certified circulating tumor
HPV deoxyribonucleic acid (ctHPVDNA) assay can be used if tissue sample is not
available.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3.
- Platelet count ≥ 100,000/mm^3.
- Hemoglobin (Hgb) ≥ 9 g/dL (if < 9 g/dL, then transfusions are acceptable to increase
hemoglobin above 9 g/dL).
- Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine
clearance ≥ 30 mL/min using the Cockcroft-Gault formula for participant with
creatinine levels > 1.5 x institutional ULN.
- Total bilirubin ≤ 1.5 x ULN OR direct bilirubin < ULN for participant with total
bilirubin > 1.5 x institutional ULN.
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT])
≤ 3.0 x ULN unless liver metastases are present in which case < 5.0 x ULN.
- Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic, and teratogenic effects.
- Therefore, for women of childbearing potential only, a negative pregnancy test
done ≤ 7 days prior to registration is required.
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen should be included.
- For treated/stable brain metastases: Patients with treated brain metastases are
eligible if follow-up brain imaging after central nervous system (CNS)-directed
therapy shows no evidence of progression.
- Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate CNS specific treatment is not required and is unlikely to be required
during the first cycle of therapy.
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months prior to registration are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
- Patients does not have a history of active myocarditis.
- Patients does not have a history of any form of pneumonitis or diffuse idiopathic or
immune mediated interstitial pulmonary disease.
- Patient does not have a history of solid organ transplantation.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm 1 (pembrolizumab) |
Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT or MRI throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. |
|
|
Experimental Arm 2 (cetuximab, pembrolizumab) |
Patients receive cetuximab IV over 120 minutes on day -14 prior to cycle 1 and then on days 1, 15 and 29 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT or MRI throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. |
|
Recruiting Locations
Kansas City, Kansas 66160
Westwood, Kansas 66205
Kansas City, Missouri 64154
Overland Park, Kansas 66210
Overland Park, Kansas 66211
Lee's Summit, Missouri 64064
More Details
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Study Contact
Detailed Description
PRIMARY OBJECTIVE: I. To assess whether the combination of cetuximab and pembrolizumab (arm 2) compared to pembrolizumab alone (arm 1) results in improved overall survival (OS) in subjects with platinum refractory HNSCC. SECONDARY OBJECTIVES: I. To compare pembrolizumab + cetuximab (arm 2) versus (vs.) pembrolizumab alone (arm 1) with respect to objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. II. To compare pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1) with respect to progression free survival (PFS) per RECIST 1.1. III. To evaluate pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1) with respect to duration of response (DOR) per RECIST 1.1. IV. To assess the safety and tolerability of pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1). V. To assess the patient-reported toxicity using Patient Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) of pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1). EXPLORATORY OBJECTIVES: I. To identify specific mutational changes that may be indicative of clinical response to pembrolizumab + cetuximab and pembrolizumab alone. II. To evaluate circulating tumor-derived deoxyribonucleic acid (ctDNA) kinetics over the course of treatment in response to pembrolizumab + cetuximab and pembrolizumab alone. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. ARM 2: Patients receive cetuximab IV over 120 minutes on day -14 prior to cycle 1 and then on days 1, 15 and 29 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT or MRI throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. After completion of study treatment, patients are followed up within 4 weeks and then every 3 and/or 6 months for up to 5 years.