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

Registration Number
NCT06589804
Lead Sponsor
National Cancer Institute (NCI)
Brief 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 i...

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:
...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
158
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.

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1 (pembrolizumab)Positron Emission TomographyPatients 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.
Arm 2 (cetuximab, pembrolizumab)Biospecimen CollectionPatients 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.
Arm 1 (pembrolizumab)PembrolizumabPatients 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.
Arm 1 (pembrolizumab)Biospecimen CollectionPatients 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.
Arm 1 (pembrolizumab)Computed TomographyPatients 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.
Arm 1 (pembrolizumab)Magnetic Resonance ImagingPatients 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.
Arm 2 (cetuximab, pembrolizumab)CetuximabPatients 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.
Arm 2 (cetuximab, pembrolizumab)Computed TomographyPatients 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.
Arm 2 (cetuximab, pembrolizumab)Magnetic Resonance ImagingPatients 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.
Arm 2 (cetuximab, pembrolizumab)PembrolizumabPatients 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.
Arm 2 (cetuximab, pembrolizumab)Positron Emission TomographyPatients 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.
Primary Outcome Measures
NameTimeMethod
Overall survivalTime from randomization to death from any cause, assessed up to 5 years

Will be estimated using the Kaplan-Meier method. Will be based on the stratified log-rank test that will compare the distributions across the treatment arms. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well, where the multivariable Cox model will also adjust for other key bas...

Secondary Outcome Measures
NameTimeMethod
Confirmed response rateUp to 5 years

Will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria if patients have a partial or complete response for 2 consecutive evaluations at least 4 weeks apart, using local review only. The proportion of patients with a confirmed response will be calculated and compared between the 2 arms using a Chi-square or Fisher's Exact test...

Duration of responseFrom the date at which the patient's earliest best objective status is first noted to be either a complete response (CR) or partial response (PR) to the earliest date progression is documented, assessed up to 5 years

Will be defined for all evaluable patients who have achieved an objective response. Will be assessed per RECIST 1.1 criteria. Will be compared between the 2 arms using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

Progression free survivalTime from randomization to the first of either disease progression or death from any cause, assessed up to 5 years

Disease progression will be assessed per RECIST 1.1 criteria. Will be compared between the 2 arms using the Kaplan-Meier method, where the log-rank test will be used to calculate the p-value.

Incidence of adverse eventsUp to 5 years

Will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

Patient-reported toxicityUp to 5 years

Will be assessed using Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE). The frequency and proportion of patients with a maximum post-baseline score greater than 0 will be compared across arms using a Chi-square or Fisher's exact test with a nominal significance level of alpha = 0.10. Similarly, the frequency and proportion of patients with a maxim...

Trial Locations

Locations (18)

Benefis Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Saint Alphonsus Cancer Care Center-Boise

🇺🇸

Boise, Idaho, United States

Saint Alphonsus Cancer Care Center-Caldwell

🇺🇸

Caldwell, Idaho, United States

Kootenai Health - Coeur d'Alene

🇺🇸

Coeur d'Alene, Idaho, United States

Saint Alphonsus Cancer Care Center-Nampa

🇺🇸

Nampa, Idaho, United States

Kootenai Clinic Cancer Services - Post Falls

🇺🇸

Post Falls, Idaho, United States

Kootenai Clinic Cancer Services - Sandpoint

🇺🇸

Sandpoint, Idaho, United States

Mary Greeley Medical Center

🇺🇸

Ames, Iowa, United States

McFarland Clinic - Ames

🇺🇸

Ames, Iowa, United States

McFarland Clinic - Boone

🇺🇸

Boone, Iowa, United States

Mercy Hospital

🇺🇸

Cedar Rapids, Iowa, United States

Oncology Associates at Mercy Medical Center

🇺🇸

Cedar Rapids, Iowa, United States

McFarland Clinic - Trinity Cancer Center

🇺🇸

Fort Dodge, Iowa, United States

McFarland Clinic - Jefferson

🇺🇸

Jefferson, Iowa, United States

McFarland Clinic - Marshalltown

🇺🇸

Marshalltown, Iowa, United States

Alliance for Clinical Trials in Oncology

🇺🇸

Boston, Massachusetts, United States

Community Medical Center

🇺🇸

Missoula, Montana, United States

Saint Alphonsus Cancer Care Center-Ontario

🇺🇸

Ontario, Oregon, United States

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