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

Phase 2

Recruiting

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

Interventions: Procedure: Biospecimen Collection
Biological: Bevacizumab
Biological: Atezolizumab
Drug: Carboplatin
Biological: Cetuximab
Drug: Cisplatin
Procedure: Computed Tomography
Drug: Docetaxel
Procedure: Echocardiography
Procedure: Magnetic Resonance Imaging
Procedure: Positron Emission Tomography

Registration Number: NCT05063552

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

Detailed Description: PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) of patients treated with chemotherapy plus cetuximab, chemotherapy plus bevacizumab, and atezolizumab plus bevacizumab. (Phase II) II. To evaluate the overall survival (OS) of patients treated with chemotherapy plus cetuximab to the superior arm from the phase II portion of the protocol. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate the OS for the subset of patients with high PD-L1 expression, defined as combined positive score (CPS) \>= 20% on all arms of treatment.

II. To evaluate the toxicity of each arm of treatment.

IMAGING OBJECTIVES:

I. To establish the correlation between fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET) and computed tomography (CT) neck imaging biomarkers (maximum standard uptake value \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\], tumor volume) and expression of PD-L1 expression (Low versus high, defined as CPS \< 20 versus CPS \>= 20).

II. To determine if 18FDG-PET/CT and CT neck imaging biomarkers at baseline will predict treatment response at nine to twelve weeks post the initiation of treatment, PFS, and OS.

EXPLORATORY OBJECTIVE:

I. To establish the correlation between 18F-FDG PET and CT neck radiomics features and PD-L1 expressions (Low versus high - defined as CPS \< 20 versus CPS \>= 20).

OUTLINE: This is a randomized phase II trial followed by a randomized phase III trial.

PHASE II: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or magnetic resonance imaging (MRI) throughout the trial. Patients may undergo echocardiography (ECHO) during screening.

ARM B: Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

ARM C: Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

PHASE III: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

ARM B: Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months if patient is \< 2 years from randomization and every 6 months if patient is 2-5 years from randomization.

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 430

Inclusion Criteria

Patient must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) (excluding 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 (Persantine), 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 combined positive score (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
Patient must not have an active autoimmune disease that requires systemic treatment within 2 years prior to randomization. Patients who are receiving replacement therapy for adrenal or pituitary insufficiency will not be excluded
Patient must not have had a severe hypersensitivity reaction to any of the drug components used on this protocol or to chimeric or humanized antibodies or fusion proteins
Patient must not have received any live vaccine within 30 days prior to randomization and while participating in the study (and continue for 5 months after the last dose of atezolizumab on Arm C). Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist (registered trademark) are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events
Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
- All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
- A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 2 months after the last dose of treatment for patients assigned to Arm A and for 6 months after the last dose of protocol treatment for patients assigned to Arms B or C.
- NOTE: Patients must also not breastfeed while on treatment and for 2 months after the last dose of treatment for patients assigned to Arm A and for 6 months after the last dose of treatment for patients assigned to Arms B or C
Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
Leukocytes >= 3,000/mcL (must be obtained =< 14 days prior to protocol randomization)
Absolute neutrophil count (ANC) >= 1,500/mcL (must be obtained =< 14 days prior to protocol randomization)
Platelets >= 100,000/mcL (must be obtained =< 14 days prior to protocol randomization)
Hemoglobin (Hgb) > 9 g/dL (must be obtained =< 14 days prior to protocol randomization) (Note: Patient may be transfused to meet this criteria)
Total bilirubin =< 2.0 x institutional upper limit of normal (ULN) (=< 5.0 x institutional ULN if hepatic metastases present or =< 3 x ULN for patients with known Gilbert's disease) (must be obtained =< 14 days prior to protocol randomization)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (< 5.0 x institutional ULN if hepatic metastases present) (must be obtained =< 14 days prior to protocol randomization)
Alkaline phosphatase < 2.5 x institutional ULN (< 5.0 x institutional ULN if hepatic or bone metastases present) (must be obtained =< 14 days prior to protocol randomization)
Creatinine =< 1.5 x institutional ULN (must be obtained =< 14 days prior to protocol randomization)
Patients with uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN) must have their calcium levels corrected prior to randomization
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization 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 treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients must not have untreated brain metastases or leptomeningeal disease
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 are eligible for this trial
Patients must not have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients may have indwelling catheters (e.g., PleurX [registered trademark])
Patient must not have significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to randomization, or unstable arrhythmia or unstable angina at the time of randomization
Patient must not receive any other chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiation therapy, or experimental medications while on protocol treatment. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization and patients must be recovered from the effects of radiation (there is no required minimum recovery period
Patient must not have had a surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to randomization, or anticipation of need for major surgical procedure while on protocol treatment
Patient must not have any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the agents used in this protocol, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Patient must not have a history of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Biospecimen Collection	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Carboplatin	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Cetuximab	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Cisplatin	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Computed Tomography	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Docetaxel	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Echocardiography	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Magnetic Resonance Imaging	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Echocardiography	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)	Positron Emission Tomography	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Bevacizumab	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Biospecimen Collection	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Carboplatin	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Cisplatin	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Echocardiography	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Computed Tomography	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Docetaxel	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Echocardiography	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Magnetic Resonance Imaging	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)	Positron Emission Tomography	Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Atezolizumab	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Magnetic Resonance Imaging	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Bevacizumab	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Biospecimen Collection	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Computed Tomography	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Echocardiography	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Magnetic Resonance Imaging	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase II, Arm C (Bevacizumab, Atezolizumab)	Positron Emission Tomography	Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Biospecimen Collection	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Positron Emission Tomography	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Carboplatin	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Cetuximab	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Cisplatin	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Computed Tomography	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Docetaxel	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Magnetic Resonance Imaging	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)	Positron Emission Tomography	Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Atezolizumab	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Bevacizumab	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Carboplatin	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Cisplatin	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Computed Tomography	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)	Docetaxel	Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS) (Phase II)	Time from treatment initiation until disease progression or death, assessed up to 5 years from randomization
Overall survival (OS) (Phase III)	Time from treatment initiation until death from any cause, assessed up to 5 years from randomization	Will be compared using a stratified log rank test.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events (Phase III)	Up to 30 days after completion of treatment
Prediction of treatment response	Baseline up to 12 weeks	Determined by 18FDG-PET/CT and CT neck imaging biomarkers. To determine if 18FDG-PET/CT and CT neck imaging biomarkers at baseline will predict treatment response at nine to twelve weeks post-treatment, PFS, and OS Logistic regression model will be fit to assess the association of the 18F -FDG PET /CT imaging biomarkers (e.g., SUVmax, MTV, TLG, tumor heterogeneity, tumor volume) with binary treatment response at 9-12 weeks post treatment. Cox proportional hazards models will be fit to assess the association of 18F -FDG PET /CT imaging biomarkers with time-to-event outcomes (PFS or OS).
OS in the subset of patients with high PD-L1 expression (Phase III)	Up to 5 years from randomization	The interaction of PD-L1 by treatment will also be evaluated in a Cox proportional hazards model.
Correlation between fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET) and computed tomography (CT) neck imaging biomarkers	Up to 5 years from randomization	The two-sample t-test will be used to compare the difference of baseline 18F -FDG PET /CT imaging biomarkers (maximum standardized uptake value \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\], tumor volume) between low and high expression of PD-L1.

Trial Locations

Locations (158): University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
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
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
MedStar Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸
Deerfield Beach, Florida, United States
Broward Health Medical Center
🇺🇸
Fort Lauderdale, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
🇺🇸
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
🇺🇸
Plantation, Florida, United States
Emory University Hospital Midtown
🇺🇸
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Hawaii Cancer Care - Westridge
🇺🇸
'Aiea, Hawaii, United States
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸
Honolulu, Hawaii, United States
Queen's Cancer Cenrer - POB I
🇺🇸
Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
Queen's Cancer Center - Kuakini
🇺🇸
Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
🇺🇸
Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸
Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸
Nampa, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸
Twin Falls, Idaho, United States
Rush - Copley Medical Center
🇺🇸
Aurora, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
University of Illinois
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸
Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸
Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Carle Physician Group-Effingham
🇺🇸
Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸
Effingham, Illinois, United States
Ingalls Memorial Hospital
🇺🇸
Harvey, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸
Mattoon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸
New Lenox, Illinois, United States
University of Chicago Medicine-Orland Park
🇺🇸
Orland Park, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸
Yorkville, Illinois, United States
Mary Greeley Medical Center
🇺🇸
Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸
Ames, Iowa, United States
Mission Cancer and Blood - Ankeny
🇺🇸
Ankeny, Iowa, United States
McFarland Clinic - Boone
🇺🇸
Boone, Iowa, United States
Mercy Cancer Center-West Lakes
🇺🇸
Clive, Iowa, United States
Mission Cancer and Blood - West Des Moines
🇺🇸
Clive, Iowa, United States
Greater Regional Medical Center
🇺🇸
Creston, Iowa, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Mission Cancer and Blood - Des Moines
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Mission Cancer and Blood - Laurel
🇺🇸
Des Moines, 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
Mercy Medical Center-West Lakes
🇺🇸
West Des Moines, Iowa, United States
University Medical Center New Orleans
🇺🇸
New Orleans, Louisiana, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Greater Baltimore Medical Center
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
UPMC Western Maryland
🇺🇸
Cumberland, Maryland, United States
UMass Memorial Medical Center - University Campus
🇺🇸
Worcester, Massachusetts, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸
Lebanon, New Hampshire, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Memorial Medical Center - Las Cruces
🇺🇸
Las Cruces, New Mexico, United States
Southeastern Medical Oncology Center-Clinton
🇺🇸
Clinton, North Carolina, United States
Southeastern Medical Oncology Center-Goldsboro
🇺🇸
Goldsboro, North Carolina, United States
Southeastern Medical Oncology Center-Jacksonville
🇺🇸
Jacksonville, North Carolina, United States
Miami Valley Hospital South
🇺🇸
Centerville, Ohio, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Premier Blood and Cancer Center
🇺🇸
Dayton, Ohio, United States
Dayton Physician LLC - Englewood
🇺🇸
Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸
Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Miami Valley Cancer Care and Infusion
🇺🇸
Greenville, Ohio, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Trinity's Tony Teramana Cancer Center
🇺🇸
Steubenville, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸
Toledo, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸
Clackamas, Oregon, United States
Providence Newberg Medical Center
🇺🇸
Newberg, Oregon, United States
Providence Portland Medical Center
🇺🇸
Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸
Portland, Oregon, United States
UPMC Altoona
🇺🇸
Altoona, Pennsylvania, United States
UPMC-Heritage Valley Health System Beaver
🇺🇸
Beaver, Pennsylvania, United States
UPMC Hillman Cancer Center at Butler Health System
🇺🇸
Butler, Pennsylvania, United States
UPMC Camp Hill
🇺🇸
Camp Hill, Pennsylvania, United States
Carlisle Regional Cancer Center
🇺🇸
Carlisle, Pennsylvania, United States
UPMC Hillman Cancer Center - Passavant - Cranberry
🇺🇸
Cranberry Township, Pennsylvania, United States
UPMC Hillman Cancer Center Erie
🇺🇸
Erie, Pennsylvania, United States
UPMC Cancer Center at UPMC Horizon
🇺🇸
Farrell, Pennsylvania, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
🇺🇸
Greensburg, Pennsylvania, United States
Oncology Hematology Associates
🇺🇸
Greenville, Pennsylvania, United States
UPMC Hillman Cancer Center in Greenville/UPMC Horizon
🇺🇸
Greenville, Pennsylvania, United States
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
🇺🇸
Harrisburg, Pennsylvania, United States
IRMC Cancer Center
🇺🇸
Indiana, Pennsylvania, United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
🇺🇸
Johnstown, Pennsylvania, United States
UPMC Cancer Center at UPMC McKeesport
🇺🇸
McKeesport, Pennsylvania, United States
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
🇺🇸
Mechanicsburg, Pennsylvania, United States
Forbes Hospital
🇺🇸
Monroeville, Pennsylvania, United States
UPMC Hillman Cancer Center - Monroeville
🇺🇸
Monroeville, Pennsylvania, United States
UPMC Hillman Cancer Center in Coraopolis
🇺🇸
Moon, Pennsylvania, United States
UPMC Hillman Cancer Center - Part of Frick Hospital
🇺🇸
Mount Pleasant, Pennsylvania, United States
Arnold Palmer Cancer Center Medical Oncology Norwin
🇺🇸
N. Huntingdon, Pennsylvania, United States
UPMC Cancer Center-Natrona Heights
🇺🇸
Natrona Heights, Pennsylvania, United States
UPMC Hillman Cancer Center - New Castle
🇺🇸
New Castle, Pennsylvania, United States
ECOG-ACRIN Cancer Research Group
🇺🇸
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Jefferson Torresdale Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC-Saint Margaret
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC-Mercy Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC-Passavant Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC-Saint Clair Hospital Cancer Center
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC Cancer Center at UPMC Northwest
🇺🇸
Seneca, Pennsylvania, United States
UPMC Cancer Center-Uniontown
🇺🇸
Uniontown, Pennsylvania, United States
UPMC Cancer Center-Washington
🇺🇸
Washington, Pennsylvania, United States
UPMC West Mifflin-Cancer Center Jefferson
🇺🇸
West Mifflin, Pennsylvania, United States
Divine Providence Hospital
🇺🇸
Williamsport, Pennsylvania, United States
Asplundh Cancer Pavilion
🇺🇸
Willow Grove, Pennsylvania, United States
UPMC Memorial
🇺🇸
York, Pennsylvania, United States
Smilow Cancer Hospital Care Center - Westerly
🇺🇸
Westerly, Rhode Island, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
Thompson Cancer Survival Center
🇺🇸
Knoxville, Tennessee, United States
Thompson Cancer Survival Center - West
🇺🇸
Knoxville, Tennessee, United States
Thompson Oncology Group-Lenoir City
🇺🇸
Lenoir City, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Thompson Oncology Group-Oak Ridge
🇺🇸
Oak Ridge, Tennessee, United States
Dartmouth Cancer Center - North
🇺🇸
Saint Johnsbury, Vermont, United States
West Virginia University Charleston Division
🇺🇸
Charleston, West Virginia, United States
ProHealth D N Greenwald Center
🇺🇸
Mukwonago, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
🇺🇸
Oconomowoc, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸
Waukesha, Wisconsin, United States

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

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts