Head And Neck Cancer

EA3202



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

STATUS: Active


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.
  • 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 received prior therapy with an immune checkpoint inhibitor (ICI) in the first-line setting for recurrent/metastatic disease or in the definitive setting for locally advanced disease (for e.g., in the context of a clinical trial). 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 disease 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 (NSAIDโ€™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 NSAIDโ€™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

  • 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 Gilbertโ€™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

United States
AR
Little Rock
University of Arkansas for Medical Sciences
Contact: Site Public Contact

CA
Dublin
Epic Care-Dublin
Contact: Site Public Contact

Emeryville
Epic Care Partners in Cancer Care
Contact: Site Public Contact

Martinez
Contra Costa Regional Medical Center
Contact: Site Public Contact

Palo Alto
Stanford Cancer Institute Palo Alto
Contact: Site Public Contact
Email: ccto-office@stanford.edu

CT
Derby
Smilow Cancer Hospital-Derby Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Fairfield
Smilow Cancer Hospital Care Center-Fairfield
Contact: Site Public Contact
Email: canceranswers@yale.edu

Glastonbury
Smilow Cancer Hospital Care Center at Glastonbury
Contact: Site Public Contact
Email: canceranswers@yale.edu

Greenwich
Smilow Cancer Hospital Care Center at Greenwich
Contact: Site Public Contact
Email: canceranswers@yale.edu

Guilford
Smilow Cancer Hospital Care Center - Guilford
Contact: Site Public Contact
Email: canceranswers@yale.edu

Hartford
Smilow Cancer Hospital Care Center at Saint Francis
Contact: Site Public Contact
Email: canceranswers@yale.edu

New Haven
Yale University
Contact: Site Public Contact
Email: canceranswers@yale.edu

North Haven
Yale-New Haven Hospital North Haven Medical Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Orange
Smilow Cancer Hospital-Orange Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Stamford
Smilow Cancer Hospital Care Center at Long Ridge
Contact: Site Public Contact
Email: canceranswers@yale.edu

Torrington
Smilow Cancer Hospital-Torrington Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Trumbull
Smilow Cancer Hospital Care Center-Trumbull
Contact: Site Public Contact
Email: canceranswers@yale.edu

Waterbury
Smilow Cancer Hospital-Waterbury Care Center
Contact: Site Public Contact
Email: canceranswers@yale.edu

Waterford
Smilow Cancer Hospital Care Center - Waterford
Contact: Site Public Contact
Email: canceranswers@yale.edu

DC
Washington
MedStar Washington Hospital Center
Contact: Site Public Contact

DE
Newark
Helen F Graham Cancer Center
Contact: Site Public Contact
Email: lbarone@christianacare.org

Medical Oncology Hematology Consultants PA
Contact: Site Public Contact
Email: lbarone@christianacare.org

FL
Fort Lauderdale
Broward Health Medical Center
Contact: Site Public Contact
Email: Allison.bruce@nemours.org

GA
Atlanta
Emory University Hospital Midtown
Contact: Site Public Contact

Emory University Hospital/Winship Cancer Institute
Contact: Site Public Contact

IA
Ames
Mary Greeley Medical Center
Contact: Site Public Contact

McFarland Clinic PC - Ames
Contact: Site Public Contact
Email: ksoder@mcfarlandclinic.com

Boone
McFarland Clinic PC-Boone
Contact: Site Public Contact

Clive
Medical Oncology and Hematology Associates-West Des Moines
Contact: Site Public Contact

Mercy Cancer Center-West Lakes
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Creston
Greater Regional Medical Center
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Des Moines
Medical Oncology and Hematology Associates-Des Moines
Contact: Site Public Contact

Mercy Medical Center - Des Moines
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Mission Cancer and Blood - Laurel
Contact: Site Public Contact

Fort Dodge
McFarland Clinic PC-Trinity Cancer Center
Contact: Site Public Contact

Jefferson
McFarland Clinic PC-Jefferson
Contact: Site Public Contact

Marshalltown
McFarland Clinic PC-Marshalltown
Contact: Site Public Contact

West Des Moines
Mercy Medical Center-West Lakes
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

ID
Boise
Saint Luke's Cancer Institute - Boise
Contact: Site Public Contact
Email: eslinget@slhs.org

Fruitland
Saint Luke's Cancer Institute - Fruitland
Contact: Site Public Contact
Email: eslinget@slhs.org

Meridian
Saint Luke's Cancer Institute - Meridian
Contact: Site Public Contact
Email: eslinget@slhs.org

Nampa
Saint Luke's Cancer Institute - Nampa
Contact: Site Public Contact
Email: eslinget@slhs.org

Twin Falls
Saint Luke's Cancer Institute - Twin Falls
Contact: Site Public Contact
Email: eslinget@slhs.org

IL
Aurora
Rush - Copley Medical Center
Contact: Site Public Contact
Email: Cancer.Research@rushcopley.com

Chicago
John H Stroger Jr Hospital of Cook County
Contact: Site Public Contact

University of Chicago Comprehensive Cancer Center
Contact: Site Public Contact
Email: cancerclinicaltrials@bsd.uchicago.edu

University of Illinois
Contact: Site Public Contact

Danville
Carle at The Riverfront
Contact: Site Public Contact
Email: Research@Carle.com

Effingham
Carle Physician Group-Effingham
Contact: Site Public Contact
Email: Research@carle.com

Mattoon
Carle Physician Group-Mattoon/Charleston
Contact: Site Public Contact
Email: Research@carle.com

New Lenox
UC Comprehensive Cancer Center at Silver Cross
Contact: Site Public Contact
Email: cancerclinicaltrials@bsd.uchicago.edu

Orland Park
University of Chicago Medicine-Orland Park
Contact: Site Public Contact
Email: cancerclinicaltrials@bsd.uchicago.edu

Urbana
Carle Cancer Center
Contact: Site Public Contact
Email: Research@carle.com

Yorkville
Rush-Copley Healthcare Center
Contact: Site Public Contact
Email: Cancer.Research@rushcopley.com

MA
Worcester
UMass Memorial Medical Center - University Campus
Contact: Site Public Contact
Email: cancer.research@umassmed.edu

MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
Contact: Site Public Contact
Email: jhcccro@jhmi.edu

Cumberland
UPMC Western Maryland
Contact: Site Public Contact

MN
Minneapolis
Abbott-Northwestern Hospital
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

Saint Louis Park
Park Nicollet Clinic - Saint Louis Park
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

Saint Paul
Regions Hospital
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

NC
Clinton
Southeastern Medical Oncology Center-Clinton
Contact: Site Public Contact
Email: jfields@cancersmoc.com

Goldsboro
Southeastern Medical Oncology Center-Goldsboro
Contact: Site Public Contact
Email: jfields@cancersmoc.com

Jacksonville
Southeastern Medical Oncology Center-Jacksonville
Contact: Site Public Contact
Email: jfields@cancersmoc.com

NH
Lebanon
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Contact: Site Public Contact
Email: cancer.research.nurse@dartmouth.edu

NM
Albuquerque
University of New Mexico Cancer Center
Contact: Site Public Contact
Email: HSC-ClinicalTrialInfo@salud.unm.edu

Las Cruces
Memorial Medical Center - Las Cruces
Contact: Site Public Contact
Email: Kim.Hoffman@lpnt.net

OH
Centerville
Miami Valley Hospital South
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Dayton
Dayton Blood and Cancer Center
Contact: Site Public Contact

Miami Valley Hospital
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital North
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Franklin
Atrium Medical Center-Middletown Regional Hospital
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Steubenville
Trinity's Tony Teramana Cancer Center
Contact: Site Public Contact

Toledo
Toledo Clinic Cancer Centers-Toledo
Contact: Site Public Contact

Troy
Upper Valley Medical Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

OK
Oklahoma City
University of Oklahoma Health Sciences Center
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

OR
Clackamas
Providence Cancer Institute Clackamas Clinic
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Newberg
Providence Newberg Medical Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Portland
Providence Portland Medical Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

PA
Altoona
UPMC Altoona
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Beaver
UPMC-Heritage Valley Health System Beaver
Contact: Site Public Contact
Email: haneydl@upmc.edu

Butler
UPMC Hillman Cancer Center at Butler Health System
Contact: Site Public Contact
Email: haneydl@upmc.edu

Camp Hill
UPMC Camp Hill
Contact: Site Public Contact

Carlisle
Carlisle Regional Cancer Center
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Cranberry Township
UPMC Hillman Cancer Center - Passavant - Cranberry
Contact: Site Public Contact
Email: haneydl@upmc.edu

Erie
UPMC Hillman Cancer Center Erie
Contact: Site Public Contact
Email: haneydl@upmc.edu

Farrell
UPMC Cancer Center at UPMC Horizon
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Greensburg
UPMC Cancer Centers - Arnold Palmer Pavilion
Contact: Site Public Contact

Greenville
Oncology Hematology Associates
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Harrisburg
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Contact: Site Public Contact
Email: klitchfield@PINNACLEHEALTH.org

Indiana
IRMC Cancer Center
Contact: Site Public Contact
Email: haneydl@upmc.edu

Johnstown
UPMC-Johnstown/John P. Murtha Regional Cancer Center
Contact: Site Public Contact

McKeesport
UPMC Cancer Center at UPMC McKeesport
Contact: Site Public Contact

Mechanicsburg
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Contact: Site Public Contact
Email: haneydl@upmc.edu

Monroeville
UPMC Hillman Cancer Center - Monroeville
Contact: Site Public Contact
Email: haneydl@upmc.edu

Moon Township
UPMC Hillman Cancer Center in Coraopolis
Contact: Site Public Contact
Email: haneydl@upmc.edu

Mount Pleasant
UPMC Hillman Cancer Center - Part of Frick Hospital
Contact: Site Public Contact
Email: haneydl@upmc.edu

Natrona Heights
UPMC Cancer Center-Natrona Heights
Contact: Site Public Contact

New Castle
UPMC Hillman Cancer Center - New Castle
Contact: Site Public Contact
Email: haneydl@upmc.edu

North Huntingdon
Arnold Palmer Cancer Center Medical Oncology Norwin
Contact: Site Public Contact
Email: haneydl@upmc.edu

Philadelphia
ECOG-ACRIN Cancer Research Group
Contact: Aarti Bhatia
Email: aarti.bhatia@yale.edu

Jefferson Torresdale Hospital
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

Thomas Jefferson University Hospital
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

Pittsburgh
Allegheny General Hospital
Contact: Site Public Contact

UPMC-Mercy Hospital
Contact: Site Public Contact

UPMC-Passavant Hospital
Contact: Site Public Contact

UPMC-Saint Clair Hospital Cancer Center
Contact: Site Public Contact

UPMC-Saint Margaret
Contact: Site Public Contact

University of Pittsburgh Cancer Institute (UPCI)
Contact: Site Public Contact

Seneca
UPMC Cancer Center at UPMC Northwest
Contact: Site Public Contact

Uniontown
UPMC Cancer Center-Uniontown
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Washington
UPMC Cancer Center-Washington
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

West Mifflin
UPMC West Mifflin-Cancer Center Jefferson
Contact: Site Public Contact

Williamsport
Divine Providence Hospital
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Willow Grove
Asplundh Cancer Pavilion
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

York
UPMC Memorial
Contact: Site Public Contact

RI
Westerly
Smilow Cancer Hospital Care Center - Westerly
Contact: Site Public Contact
Email: canceranswers@yale.edu

TN
Knoxville
Thompson Cancer Survival Center
Contact: Site Public Contact

Thompson Cancer Survival Center - West
Contact: Site Public Contact

Lenoir City
Thompson Oncology Group-Lenoir City
Contact: Site Public Contact

Nashville
Vanderbilt University/Ingram Cancer Center
Contact: Site Public Contact

Oak Ridge
Thompson Oncology Group-Oak Ridge
Contact: Site Public Contact

VT
Saint Johnsbury
Norris Cotton Cancer Center-North
Contact: Site Public Contact
Email: cancer.research.nurse@hitchcock.org

WI
Mukwonago
ProHealth D N Greenwald Center
Contact: Site Public Contact
Email: research.institute@phci.org

Oconomowoc
ProHealth Oconomowoc Memorial Hospital
Contact: Site Public Contact

Waukesha
UW Cancer Center at ProHealth Care
Contact: Site Public Contact
Email: Chanda.miller@phci.org

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.

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.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.


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ECOG-ACRIN Cancer Research Group