Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers

Running, not enrolling · Phase 2/Phase 3

Conditions studied: Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Lip and Oral Cavity Carcinoma, Metastatic Nasal Cavity Squamous Cell Carcinoma, Metastatic Nasopharyngeal Squamous Cell Carcinoma, Metastatic Pharyngeal Squamous Cell Carcinoma, Metastatic Sinonasal Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Lip and Oral Cavity Squamous Cell Carcinoma, Recurrent Nasopharyngeal Squamous Cell Carcinoma, Recurrent Pharyngeal Squamous Cell Carcinoma, Recurrent Sinonasal Squamous Cell Carcinoma, Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma 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 Nasopharyngeal Carcinoma AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IV Sinonasal Cancer AJCC v8

In brief

This phase II/III compares the standard therapy (chemotherapy plus cetuximab) versus adding bevacizumab to standard chemotherapy, versus combination of just bevacizumab and atezolizumab in treating patients with head and neck cancer that has spread to other places in the body (metastatic or advanced stage) or has come back after prior treatment (recurrent). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Cisplatin and carboplatin are in a class of chemotherapy medications known as platinum-containing compounds. They work by killing, stopping, or slowing the growth of cancer cells. Docetaxel is in a class of chemotherapy medications called taxanes. It stops cancer cells from growing and dividing and may kill them. The addition of bevacizumab to standard chemotherapy or combination therapy with bevacizumab and atezolizumab may be better than standard chemotherapy plus cetuximab in treating patients with recurrent/metastatic head and neck cancers.

Key facts

Study ID

NCT05063552

Run by

National Cancer Institute (NCI)

People needed

430

Starts

2023-03-13

Expected to finish

2027-12-15

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patient must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) (excluding squamous cell carcinoma [SCC] of salivary glands, Epstein-Barr virus [EBV]-associated nasopharynx and skin)
• Patient must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Measurements must be obtained within 4 weeks prior to randomization
• Patient must be >= 18 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have disease progression after prior therapy with an immune checkpoint inhibitor (ICI) in the first-line setting for recurrent/metastatic disease. Patient must have received first-line immune checkpoint inhibition for at least 6 weeks. Patients who have recurred or progressed within 12 weeks of immune checkpoint inhibition administered in the definitive setting for locally advanced disease (for e.g., in the context of a clinical trial) will also be eligible if local therapies are not feasible
• Prior combination immunotherapies are permitted, but patient must not have had prior antiangiogenic treatment (e.g., bevacizumab, ziv-aflibercept, ramucirumab, sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib, etc.). Patient must have completed any prior investigational therapy at least 28 days prior to randomization.
• NOTE: Patients who received platinum/taxanes in the locally-advanced or recurrent/metastatic setting and did not progress for at least 4 months thereafter, will be eligible for this study. Patients who received cetuximab in the locally-advanced setting and did not progress for at least 4 months thereafter, will also be eligible for this study
• Patient must not have a history of >= grade 3 immune-related adverse event on prior ICI therapy (except those that could be managed with steroids [e.g., dermatologic toxicity, asymptomatic elevation of pancreatic enzymes, etc.]) and ICI could eventually be resumed. Patients who developed grade 3 endocrinopathies but are now stable on hormone supplementation and/or a daily prednisone dose of =< 10 mg (or equivalent doses of another glucocorticoid), will be permitted on this trial
• Patient must not have a history of PD-1 inhibitor-induced hyper-progression, defined as 100% increase in tumor burden within 8 weeks (or 50% within 4 weeks) of initiating ICI and associated with clinical deterioration
• Patient must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with bevacizumab therapy:
• Prior carotid bleeding,
• Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies,
• Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies,
• Any prior history of bleeding related to the current head and neck cancer,
• History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode of coughing) within 3 months prior to randomization
• Patient must not have uncontrolled hypertension, a history of hypertensive crisis or hypertensive encephalopathy, or a history of grade 4 thromboembolism
• Patient must not have a history of coagulopathy or hemorrhagic disorders
• Patient must not have a history of thrombosis (e.g., pulmonary embolism or deep venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use of anticoagulation is allowed)
• Patient must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents (NSAID's) known to inhibit platelet function. The use of anti-platelet agents [e.g., dipyridamole (Persatine), ticlopidine (Ticlid), clopidogrel (Plavix)] is allowed only if patient is not receiving concurrent aspirin or NSAID's known to inhibit platelet function
• Patient must have PD-L1 expression >= 1% by CPS in the tumor and/or immune cells
• NOTE: Enrolling centers should test for PD-L1 CPS preferably using the SP263 assay. Where this is not feasible, using their preferred Clinical Laboratory Improvement Act (CLIA)-certified or similar assay will be accepted. It is preferred for standard of care (SOC) PD-L1 assessments to be done on post-first line ICI samples if available, but SOC PD-L1 assessments on pre-ICI samples will be accepted for eligibility
• Patient must not have a severe infection within 4 weeks prior to randomization, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Patients must not have active tuberculosis
• Patient must not have a history of non-infectious pneumonitis requiring steroids at doses greater than or equal to 10 mg per day of prednisone or the equivalent on first line immunotherapy
• Patient must not have a history of solid organ transplantation or stem-cell transplant
• Patient must not be on immunosuppressive medication within 7 days prior to randomization except for: intranasal, inhaled, or topical steroids, local steroid injection, systemic corticosteroids at doses less than or equal to 10 mg per day of prednisone or the equivalent, or steroids used as premedication for hypersensitivity reactions

Where it is running

• Epic Care-Dublin — Dublin, California, United States
• Epic Care Partners in Cancer Care — Emeryville, California, United States
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States
• Contra Costa Regional Medical Center — Martinez, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• VA Palo Alto Health Care System — Palo Alto, California, United States
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States
• Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States
• Smilow Cancer Hospital Care Center at Glastonbury — Glastonbury, Connecticut, United States
• Smilow Cancer Hospital Care Center at Greenwich — Greenwich, Connecticut, United States
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States
• Smilow Cancer Hospital Care Center at Saint Francis — Hartford, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Yale-New Haven Hospital North Haven Medical Center — North Haven, Connecticut, United States
• Smilow Cancer Hospital-Orange Care Center — Orange, Connecticut, United States
• McFarland Clinic - Ames — Ames, Iowa, United States
• Smilow Cancer Hospital Care Center at Long Ridge — Stamford, Connecticut, United States
• Smilow Cancer Hospital-Torrington Care Center — Torrington, Connecticut, United States
• Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States
• Smilow Cancer Hospital-Waterbury Care Center — Waterbury, Connecticut, United States
• Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States
• Helen F Graham Cancer Center — Newark, Delaware, United States
• Medical Oncology Hematology Consultants PA — Newark, Delaware, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States

Full record on ClinicalTrials.gov

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