AzTrials
AzTrials

Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Phase 2/3NCT05063552

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

A Phase 2/3 study testing Atezolizumab, Bevacizumab and Biospecimen Collection in people with Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Metastatic Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 172 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Bevacizumab and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
430 participants
Where
172 sitesUnited States
Study dates
13 Mar 2023to 15 Dec 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • 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]) and 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

Who cannot join

None listed.

Trial locations and contacts

172 sites in 1 country.

172 sites in 1 country

United States172 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • UPMC Altoona

    Altoona, Pennsylvania, 16601

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • UPMC Hillman Cancer Center at Butler Health System

    Butler, Pennsylvania, 16001

  • UPMC Camp Hill

    Camp Hill, Pennsylvania, 17011

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Carlisle Regional Cancer Center

    Carlisle, Pennsylvania, 17015

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • UPMC Hillman Cancer Center - Passavant - Cranberry

    Cranberry Township, Pennsylvania, 16066

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • UPMC Western Maryland

    Cumberland, Maryland, 21502

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Premier Blood and Cancer Center

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Epic Care-Dublin

    Dublin, California, 94568

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Epic Care Partners in Cancer Care

    Emeryville, California, 94608

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • UPMC Cancer Center at UPMC Horizon

    Farrell, Pennsylvania, 16121

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Smilow Cancer Hospital Care Center at Glastonbury

    Glastonbury, Connecticut, 06033

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Miami Valley Cancer Care and Infusion

    Greenville, Ohio, 45331

  • UPMC Hillman Cancer Center in Greenville/UPMC Horizon

    Greenville, Pennsylvania, 16125

  • Smilow Cancer Hospital Care Center at Greenwich

    Greenwich, Connecticut, 06830

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • UPMC Pinnacle Cancer Center/Community Osteopathic Campus

    Harrisburg, Pennsylvania, 17109

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • IRMC Cancer Center

    Indiana, Pennsylvania, 15701

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

  • UPMC-Johnstown/John P. Murtha Regional Cancer Center

    Johnstown, Pennsylvania, 15901

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Covenant Health Cancer Centers

    Knoxville, Tennessee, 37916

  • Covenant Health Cancer Centers - West

    Knoxville, Tennessee, 37932

  • Memorial Medical Center-Las Cruces

    Las Cruces, New Mexico, 88011

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Covenant Health Oncology Group - Lenoir City

    Lenoir City, Tennessee, 37772

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • McFarland Clinic - Marshalltown

    Marshalltown, Iowa, 50158

  • Contra Costa Regional Medical Center

    Martinez, California, 94553-3156

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • UPMC Cancer Center at UPMC McKeesport

    McKeesport, Pennsylvania, 15132

  • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

    Mechanicsburg, Pennsylvania, 17050

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Community Medical Center

    Missoula, Montana, 59804

  • Forbes Hospital

    Monroeville, Pennsylvania, 15146

  • UPMC Hillman Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • UPMC Hillman Cancer Center in Coraopolis

    Moon Township, Pennsylvania, 15108

  • UPMC Hillman Cancer Center - Part of Frick Hospital

    Mount Pleasant, Pennsylvania, 15666

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • Arnold Palmer Cancer Center Medical Oncology Norwin

    N. Huntingdon, Pennsylvania, 15642

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • UPMC Cancer Center-Natrona Heights

    Natrona Heights, Pennsylvania, 15065

  • UPMC Hillman Cancer Center - New Castle

    New Castle, Pennsylvania, 16105

  • Yale University

    New Haven, Connecticut, 06520

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Yale-New Haven Hospital North Haven Medical Center

    North Haven, Connecticut, 06473

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • HSHS Saint Elizabeth's Hospital

    O'Fallon, Illinois, 62269

  • Covenant Health Oncology Group - Oak Ridge

    Oak Ridge, Tennessee, 37830

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Smilow Cancer Hospital-Orange Care Center

    Orange, Connecticut, 06477

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Jefferson Torresdale Hospital

    Philadelphia, Pennsylvania, 19114

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC-Saint Margaret

    Pittsburgh, Pennsylvania, 15215

  • UPMC-Mercy Hospital

    Pittsburgh, Pennsylvania, 15219

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UPMC-Saint Clair Hospital Cancer Center

    Pittsburgh, Pennsylvania, 15243

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Kootenai Clinic Cancer Services - Post Falls

    Post Falls, Idaho, 83854

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Dartmouth Cancer Center - North

    Saint Johnsbury, Vermont, 05819

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • Kootenai Clinic Cancer Services - Sandpoint

    Sandpoint, Idaho, 83864

  • UPMC Cancer Center at UPMC Northwest

    Seneca, Pennsylvania, 16346

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Mercy Hospital South

    St Louis, Missouri, 63128

  • Smilow Cancer Hospital Care Center at Long Ridge

    Stamford, Connecticut, 06902

  • Trinity's Tony Teramana Cancer Center

    Steubenville, Ohio, 43952

  • Toledo Clinic Cancer Centers-Toledo

    Toledo, Ohio, 43623

  • Smilow Cancer Hospital-Torrington Care Center

    Torrington, Connecticut, 06790

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Saint Luke's Cancer Institute - Twin Falls

    Twin Falls, Idaho, 83301

  • UPMC Cancer Center-Uniontown

    Uniontown, Pennsylvania, 15401

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • UPMC Cancer Center-Washington

    Washington, Pennsylvania, 15301

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

  • UI Health Care Mission Cancer and Blood - Waukee Clinic

    Waukee, Iowa, 50263

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Mercy Medical Center-West Lakes

    West Des Moines, Iowa, 50266

  • UPMC West Mifflin-Cancer Center Jefferson

    West Mifflin, Pennsylvania, 15122

  • Smilow Cancer Hospital Care Center - Westerly

    Westerly, Rhode Island, 02891

  • Divine Providence Hospital

    Williamsport, Pennsylvania, 17754

  • Asplundh Cancer Pavilion

    Willow Grove, Pennsylvania, 19090

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

  • UPMC Memorial

    York, Pennsylvania, 17408

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

Other trials in United States

About this study

Official title: A Phase II/III Trial of Chemotherapy + Cetuximab vs Chemotherapy + Bevacizumab vs Atezolizumab + Bevacizumab Following Progression on Immune Checkpoint Inhibition in Recurrent/Metastatic Head and Neck Cancers

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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:

  1. 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 IV 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.

Being tested
Atezolizumab, Bevacizumab, Biospecimen Collection, Carboplatin, Cetuximab
Medical subject headings
Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Mouth Neoplasms, Lymphoid Interstitial Pneumonia, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Nasopharyngeal Carcinoma, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabBiological

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • BevacizumabBiological

    Also called ABP 215, ABP-215, ABP215, Alymsys

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CetuximabBiological

    Also called C 225, C-225, C225, Cetuxa

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • DocetaxelDrug

    Also called Docecad, RP 56976, RP-56976, RP56976

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET scan

Study groups in NCT05063552
Study groupRoleWhat they receive
Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)Active comparatorPatients 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.
Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Biological: Cetuximab; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Docetaxel; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Docetaxel; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Phase II, Arm C (Bevacizumab, Atezolizumab)ExperimentalPatients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab IV 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.
Receives: Biological: Atezolizumab; Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Biological: Cetuximab; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Docetaxel; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)ExperimentalPatients receive treatment as in Arm B or C above based on results of the Phase II trial.
Receives: Biological: Atezolizumab; Biological: Bevacizumab; Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Docetaxel; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS) (Phase II)

    Measured: Time from treatment initiation until disease progression or death, assessed up to 5 years from randomization

  2. Overall survival (OS) (Phase III)

    Will be compared using a stratified log rank test.

    Measured: Time from treatment initiation until death from any cause, assessed up to 5 years from randomization

Secondary outcomes (4)

  1. OS in the subset of patients with high PD-L1 expression (Phase III)

    The interaction of PD-L1 by treatment will also be evaluated in a Cox proportional hazards model.

    Measured: Up to 5 years from randomization

  2. Incidence of adverse events (Phase III)

    Measured: Up to 30 days after completion of treatment

  3. Correlation between fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET) and computed tomography (CT) neck imaging biomarkers

    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.

    Measured: Up to 5 years from randomization

  4. Prediction of treatment response

    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).

    Measured: Baseline up to 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2021
  2. Study start13 Mar 2023
  3. Primary completion15 Dec 2027 (estimated)
  4. Study completion15 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
430 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05063552
Sponsor's protocol ID
NCI-2021-10021
Other IDs
NCI-2021-10021, EA3202, EA3202, U10CA180820
Status last verified
Oct 2026
First submitted
30 Sep 2021
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Atezolizumab, Bevacizumab and Biospecimen Collection in people with Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Metastatic Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 172 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 54 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 172 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (Phase II) (time frame: Time from treatment initiation until disease progression or death, assessed up to 5 years from randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05063552.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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