Trial Title:
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
NCT ID:
NCT06589804
Condition:
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
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Laryngeal Neoplasms
Mouth Neoplasms
Recurrence
Antineoplastic Agents, Immunological
Pembrolizumab
Cetuximab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm 1 (pembrolizumab)
Arm group label:
Arm 2 (cetuximab, pembrolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Cetuximab
Description:
Given IV
Arm group label:
Arm 2 (cetuximab, pembrolizumab)
Other name:
C 225
Other name:
C-225
Other name:
C225
Other name:
Cetuximab Biosimilar CDP-1
Other name:
Cetuximab Biosimilar CMAB009
Other name:
Cetuximab Biosimilar KL 140
Other name:
Chimeric Anti-EGFR Monoclonal Antibody
Other name:
Chimeric MoAb C225
Other name:
Chimeric Monoclonal Antibody C225
Other name:
Erbitux
Other name:
IMC-C225
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Arm 1 (pembrolizumab)
Arm group label:
Arm 2 (cetuximab, pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm 1 (pembrolizumab)
Arm group label:
Arm 2 (cetuximab, pembrolizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Arm 1 (pembrolizumab)
Arm group label:
Arm 2 (cetuximab, pembrolizumab)
Other name:
BCD-201
Other name:
GME 751
Other name:
GME751
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK 3475
Other name:
MK-3475
Other name:
MK3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
Pembrolizumab Biosimilar GME751
Other name:
Pembrolizumab Biosimilar QL2107
Other name:
QL2107
Other name:
SCH 900475
Other name:
SCH-900475
Other name:
SCH900475
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Arm 1 (pembrolizumab)
Arm group label:
Arm 2 (cetuximab, pembrolizumab)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Summary:
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.
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
November 7, 2024
Completion date:
November 30, 2029
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06589804
