Testing Docetaxel-Cetuximab or the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy and Radiation Therapy in High-Risk Head and Neck Cancer

Phase 2

Recruiting

• Conditions: Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7
• Interventions: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Atezolizumab; Drug: Cisplatin; Drug: Docetaxel; Biological: Cetuximab; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Other: Survey Administration

• Registration Number: NCT01810913
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase II/III trial studies how well radiation therapy works when given together with cisplatin, docetaxel, cetuximab, and/or atezolizumab after surgery in treating patients with high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous cell). Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. 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. The purpose of this study is to compare the usual treatment (radiation therapy with cisplatin chemotherapy) to using radiation therapy with docetaxel and cetuximab chemotherapy, and using the usual treatment plus an immunotherapy drug, atezolizumab.

Detailed Description

PRIMARY OBJECTIVES:

I. To select the better docetaxel-based experimental arm to improve disease-free survival (DFS) over the control arm of radiation and cisplatin. (Phase II) (COMPLETE AS OF 20-MAR-2020) II. To determine if the combination of docetaxel-cetuximab and intensity-modulated radiation therapy (IMRT) is superior in terms of overall survival (OS) compared to standard cisplatin and IMRT in the adjuvant treatment of pathologic high risk, human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). (Phase III) III. To determine if the combination of atezolizumab, cisplatin, and IMRT is superior in terms of OS compared to standard cisplatin and IMRT in the adjuvant treatment of pathologic high risk, HPV-negative HNSCC. (Phase III)

SECONDARY OBJECTIVES:

I. To compare disease-free survival (DFS) between each experimental arm and the control arm. (Phase III) II. To determine whether each experimental arm improves local-regional disease control and the rate of distant metastasis. (Phase III) III. To compare acute toxicity profiles between each experimental arm and the control arm. (Phase III) IV. To compare late toxicity profiles at 1, 3, and 5 years after treatment. (Phase III) V. To assess long term DFS and OS between each experimental arm and the control arm. (Phase III) VI. To compare symptom burden, as measured by the MD Anderson Symptom Inventory - Head and Neck (MDASI-HN) (primary patient reported outcome \[PRO\]), and quality of life, as measured by the Functional Assessment of Cancer Therapy - Head and Neck (FACT-H\&N) (secondary PRO), between each experimental arm and the control arm. (Phase III)

EXPLORATORY OBJECTIVE:

I. To collect blood and tissue specimens for future translational research. (Phase III)

OUTLINE: Patients are randomized to 1 of 3 arms - Phase II (Arms 1, 2 or 3) and for Phase III (Arms 1, 3 or 4).

ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) five days a week for 6 weeks and receive concurrent cisplatin intravenously (IV) over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. (CLOSED AS OF 20-MAR-2020)

ARM 3: Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and concurrently receive docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM 4: Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity.

All patients undergo collection of blood samples during screening and throughout the study and may undergo computed tomography (CT) scans and/or magnetic resonance imaging (MRI) and biopsy as clinically indicated on study.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Timeline

• Study First Submitted: 2013-03-12
• Study First Submitted QC: 2013-03-12
• Study First Posted: 2013-03-14
• Study Start: 2013-03-22
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-17
• Last Update Posted: 2025-05-20
• Primary Completion: 2027-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 613

Inclusion Criteria

• PHASE II INCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)

• Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx

• Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration; Note: patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible

• Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink)

• Pathologic stage III or IV HNSCC, including no distant metastases, based upon the following minimum diagnostic workup:

  • General history and physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration;
  • Examination by an ear nose throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
  • Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave
  • Chest CT scan (with or without contrast) or CT/PET that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement

• Zubrod performance status of 0-1 within 14 days prior to registration

• Age >= 18

• Absolute granulocyte count (AGC) >= 1,500 cells/mm^3 (obtained within 14 days prior to registration on study)

• Platelets >= 100,000 cells/mm^3 (obtained within 14 days prior to registration on study)

• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

• Total bilirubin < 2 x institutional upper limit of normal (ULN) within 14 days prior to registration

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x institutional ULN within 14 days prior to registration

• Serum creatinine institutional ULN within 14 days prior to registration or; creatinine clearance (CC) >= 50 ml/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula

• Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential

• The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator's discretion

• Patients with feeding tubes are eligible for the study

• Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control

• Patient must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for epidermal growth factor receptor (EGFR) analysis and for oropharyngeal cancer patients, human papilloma virus (HPV) analysis

• PHASE III: Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx

• PHASE III: Patients with oropharyngeal cancer must have p16-negative based on central review prior to Step 2 registration. All patients with oropharyngeal primary must consent for mandatory tissue submission for central p16 confirmation

• PHASE III: Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration

  • Note: Patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection. The gross total resection has to be done within 63 days prior to registration. If, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible

• PHASE III: Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink or tumor in a final separately submitted margin)

• PHASE III: Pathologic stage III or IV HNSCC (American Joint Committee on Cancer [AJCC] 7th edition), including no distant metastases, based upon the following minimum diagnostic workup:

  • General history and physical examination by a radiation oncologist or medical oncologist within 84 days prior to registration;
  • Examination by an ENT or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror or fiberoptic or direct procedure), if appropriate, is recommended but not required. Intra-operative examination is acceptable documentation.
  • Pre-op Imaging of the head and neck: A neck CT (with contrast and of diagnostic quality) or PET/CT (with contrast and of diagnostic quality) and/or an MRI of the neck of diagnostic quality (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in DICOM format via TRIAD. The report is to be uploaded into Rave.
  • Chest CT scan (with or without contrast) or PET/CT that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: If the PET/CT with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement

• PHASE III: Zubrod performance status of 0-1 within 14 days prior to registration

• PHASE III: Age >= 18

• PHASE III: Leukocytes >= 2,500 cells/mm^3 (obtained within 14 days prior to registration on study)

• PHASE III: Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 14 days prior to registration on study)

• PHASE III: Platelets >= 100,000 cells/mm^3 (obtained within 14 days prior to registration on study)

• PHASE III: Hemoglobin >= 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb >= 8.0 g/dL is acceptable) (obtained within 14 days prior to registration on study)

• PHASE III: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x institutional ULN may be enrolled) (within 14 days prior to registration)

• PHASE III: AST or ALT =< 3 x institutional ULN (within 14 days prior to registration)

• PHASE III: Alkaline phosphatase =< 2.5 x institutional ULN (within 14 days prior to registration)

• PHASE III: Creatinine clearance (CrCl) >= 50 mL/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula

• PHASE III: Patients with feeding tubes are eligible for the study

• PHASE III: Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential

• PHASE III: All patients must provide study specific informed consent prior to study entry

• PHASE III: Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:

  • A stable regimen of highly active anti-retroviral therapy (HAART);
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections;
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests

Exclusion Criteria

• PHASE II EXCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago

• Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible

• Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable

• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration

  • Transmural myocardial infarction within 6 months prior to registration

  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

    • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration

  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol

    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease and Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immuno-compromised patients.

• Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v.] 4):

• Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels

• Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14 mmol/L)

• Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels

• Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels

• Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic

• Prior allergic reaction to cetuximab

• PHASE III: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) with the following exceptions: T1-2, N0, M0 resected differentiated thyroid carcinoma; Note that noninvasive cancers (For example, carcinoma in situ of the breast, oral cavity, or cervix) are permitted even if diagnosed and treated < 3 years ago

• PHASE III: Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible

• PHASE III: Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy (such as anti-EGF therapy), or immune therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, a prior anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is not permitted

• PHASE III: Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• PHASE III: Severe, active co-morbidity, defined as follows:

  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification; to be eligible for this trial, patients should be class 2B or better within 6 months prior to registration

  • Transmural myocardial infarction within 6 months prior to registration;

  • Severe infections within 4 weeks prior to registration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;

  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.

  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;

  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in a prior radiation field (fibrosis) is permitted, provided that field does not overlap with the planned radiation field for the study cancer;

  • Patients with active tuberculosis (TB) are excluded;

  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease;

    • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

  • History of allogeneic bone marrow transplantation or solid organ transplantation.

  • A diagnosis of immunodeficiency:

    • Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note: HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

  • Is receiving treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to registration.

    • Note: Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
    • Note: The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.

  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

    • Patients with a history of autoimmune hypothyroidism who are asymptomatic and/or are on a stable dose of thyroid replacement hormone are eligible.
    • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
    • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
    • Rash must cover less than 10% of body surface area (BSA)
    • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
    • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)

• PHASE III: Grade 3-4 electrolyte abnormalities (CTCAE, v. 4) within 14 days prior to registration:

  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dL (1.75 mmol/L) or > 12.5 mg/dL (> 3.1 mmol/L) despite intervention to normalize levels;
  • Glucose < 40 mg/dL (< 2.2 mmol/L) or > 250 mg/dL (> 14 mmol/L);
  • Magnesium < 0.9 mg/dL (< 0.4 mmol/L) or > 3 mg/dL (> 1.23 mmol/L) despite intervention to normalize levels;
  • Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels;
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels.

• PHASE III: Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for up to 5 months from last study treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding and unwilling to discontinue are also excluded

• PHASE III: History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

• PHASE III: Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other non-oncologic reasons (e.g., osteoporosis) is allowed

• PHASE III: Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) for non-oncologic reasons who cannot discontinue it before registration

• PHASE III: Patients with known distant metastatic disease are excluded

• PHASE III: Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

• PHASE III: Major surgical procedure within 28 days prior to registration or anticipation of need for a major surgical procedure during the course of the study

• PHASE III: Administration of a live, attenuated vaccine within 4 weeks prior to registration or anticipation that such a live, attenuated vaccine will be required during the study and for patients receiving atezolizumab, up to 5 months after the last dose of atezolizumab.

  • Influenza vaccination should be given during influenza season only (approximately October to

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 (IMRT, cisplatin)	Biopsy Procedure	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 2 (IMRT, docetaxel)	Biospecimen Collection	Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Arm 1 (IMRT, cisplatin)	Biospecimen Collection	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 1 (IMRT, cisplatin)	Cisplatin	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 1 (IMRT, cisplatin)	Computed Tomography	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 1 (IMRT, cisplatin)	Intensity-Modulated Radiation Therapy	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 1 (IMRT, cisplatin)	Magnetic Resonance Imaging	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 1 (IMRT, cisplatin)	Survey Administration	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 2 (IMRT, docetaxel)	Computed Tomography	Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Arm 3 (IMRT, docetaxel, cetuximab)	Biospecimen Collection	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 2 (IMRT, docetaxel)	Docetaxel	Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Arm 2 (IMRT, docetaxel)	Intensity-Modulated Radiation Therapy	Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Arm 2 (IMRT, docetaxel)	Magnetic Resonance Imaging	Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Arm 2 (IMRT, docetaxel)	Survey Administration	Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Arm 3 (IMRT, docetaxel, cetuximab)	Biopsy Procedure	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 3 (IMRT, docetaxel, cetuximab)	Cetuximab	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 3 (IMRT, docetaxel, cetuximab)	Computed Tomography	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 3 (IMRT, docetaxel, cetuximab)	Docetaxel	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 3 (IMRT, docetaxel, cetuximab)	Intensity-Modulated Radiation Therapy	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 3 (IMRT, docetaxel, cetuximab)	Magnetic Resonance Imaging	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 3 (IMRT, docetaxel, cetuximab)	Survey Administration	Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Atezolizumab	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Biopsy Procedure	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Biospecimen Collection	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Cisplatin	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Computed Tomography	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Intensity-Modulated Radiation Therapy	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Magnetic Resonance Imaging	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Arm 4 (IMRT, cisplatin, atezolizumab)	Survey Administration	Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.

Primary Outcome Measures

Name	Time	Method
Disease-free survival (Phase II)	From date of randomization until date of local-regional recurrence, distant metastasis or death due to any cause, assessed up to 7 years	Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test.
Overall survival (Phase III)	From date of randomization to death due to any cause, assessed up to 7 years	Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test. Multivariate analysis will be performed using the Cox proportional hazards model.

Secondary Outcome Measures

Name	Time	Method
Local-regional failure	From date of randomization until date of local-regional recurrence, assessed up to 7 years	The cumulative incidence method will be used to estimate rates, and the failure rates for the experimental arms will be compared against the control using a failure-specific log rank test.
Distant metastasis	From date of randomization to date of distant metastasis, assessed up to 7 years	The cumulative incidence method will be used to estimate rates, and the failure rates for the experimental arms will be compared against the control using a failure-specific log rank test.
Toxicity	From start of treatment to death or last follow-up	Adverse events will be graded using Common Terminology Criteria for Adverse Events version 4.0. Rates of grade 3+ adverse events overall will be compared between arms by Chi-square test, or Fisher's exact test.
Patient-reported outcome, symptom burden	Time from randomization to a first recovery within at least one MID unit of total symptom severity compared to the baseline (reference) score	Time to recovery of baseline total symptom severity from the MD Anderson Symptom Inventory - Head and Neck. The cumulative incidence method will be used to estimate the event rates, and the event rates between arms will be compared using a cause-specific log rank test. The Fine-Gray subdistribution hazards model may be applied to further explore outcomes by treatment arm and other covariates.
Quality of life	Baseline and 1 year post radiation therapy	Quality of life change from baseline at 1-year post RT, as measured by the Functional Assessment of Cancer Therapy - Head and Neck (FACT) Trial Outcome Index (TOI). FACT TOI is a validated efficient summary index of physical/functional outcomes, and disease site-specific items, which is highly reliable and sensitive to change in performance status rating. A constrained longitudinal data analysis model will be fitted with all the time points (discrete), the treatment factor and its interaction. The secondary non-inferiority patient-reported outcome hypothesis will be tested using a confidence interval approach.

Trial Locations

Locations (322)

University of Alabama at Birmingham Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Banner University Medical Center - Tucson; 🇺🇸 Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus; 🇺🇸 Tucson, Arizona, United States

The Kirklin Clinic at Acton Road; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn; 🇺🇸 Auburn, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

Sutter Cancer Centers Radiation Oncology Services-Cameron Park; 🇺🇸 Cameron Park, California, United States

Mercy San Juan Medical Center; 🇺🇸 Carmichael, California, United States

UC San Diego Health System - Encinitas; 🇺🇸 Encinitas, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Memorial Medical Center; 🇺🇸 Modesto, 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

Sutter Cancer Centers Radiation Oncology Services-Roseville; 🇺🇸 Roseville, California, United States

Sutter Medical Center Sacramento; 🇺🇸 Sacramento, California, United States

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Saint Helena Hospital; 🇺🇸 Saint Helena, California, United States

UCSF Medical Center-Mount Zion; 🇺🇸 San Francisco, California, United States

UCSF Medical Center-Mission Bay; 🇺🇸 San Francisco, California, United States

Mills Health Center; 🇺🇸 San Mateo, California, United States

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Rocky Mountain Cancer Centers-Boulder; 🇺🇸 Boulder, Colorado, United States

Penrose-Saint Francis Healthcare; 🇺🇸 Colorado Springs, Colorado, United States

AdventHealth Porter; 🇺🇸 Denver, Colorado, United States

Shaw Cancer Center; 🇺🇸 Edwards, Colorado, United States

Banner North Colorado Medical Center; 🇺🇸 Greeley, Colorado, United States

Rocky Mountain Cancer Centers-Littleton; 🇺🇸 Littleton, Colorado, United States

Longmont United Hospital; 🇺🇸 Longmont, Colorado, United States

Banner McKee Medical Center; 🇺🇸 Loveland, Colorado, United States

AdventHealth Parker; 🇺🇸 Parker, Colorado, United States

University of Connecticut; 🇺🇸 Farmington, Connecticut, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford; 🇺🇸 Waterford, Connecticut, United States

Helen F Graham Cancer Center; 🇺🇸 Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

George Washington University Medical Center; 🇺🇸 Washington, District of Columbia, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach; 🇺🇸 Deerfield Beach, Florida, United States

Holy Cross Hospital; 🇺🇸 Silver Spring, Maryland, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

AdventHealth Orlando; 🇺🇸 Orlando, Florida, United States

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Augusta University Medical Center; 🇺🇸 Augusta, Georgia, United States

Memorial Health University Medical Center; 🇺🇸 Savannah, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler; 🇺🇸 Savannah, Georgia, United States

Queen's Medical Center; 🇺🇸 Honolulu, Hawaii, United States

The Cancer Center of Hawaii-Liliha; 🇺🇸 Honolulu, Hawaii, United States

Saint Alphonsus Cancer Care Center-Nampa; 🇺🇸 Nampa, Idaho, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

John H Stroger Jr Hospital of Cook County; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Illinois; 🇺🇸 Chicago, Illinois, United States

Decatur Memorial Hospital; 🇺🇸 Decatur, Illinois, United States

Crossroads Cancer Center; 🇺🇸 Effingham, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

NorthShore University HealthSystem-Glenbrook Hospital; 🇺🇸 Glenview, Illinois, United States

NorthShore University HealthSystem-Highland Park Hospital; 🇺🇸 Highland Park, Illinois, United States

HSHS Saint Elizabeth's Hospital; 🇺🇸 O'Fallon, Illinois, United States

Advocate Christ Medical Center; 🇺🇸 Oak Lawn, Illinois, United States

OSF Saint Francis Radiation Oncology at Peoria Cancer Center; 🇺🇸 Peoria, Illinois, United States

OSF Saint Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

UW Health Carbone Cancer Center Rockford; 🇺🇸 Rockford, Illinois, United States

Springfield Memorial Hospital; 🇺🇸 Springfield, Illinois, United States

Ascension Saint Vincent Anderson; 🇺🇸 Anderson, Indiana, United States

Elkhart General Hospital; 🇺🇸 Elkhart, Indiana, United States

Radiation Oncology Associates PC; 🇺🇸 Fort Wayne, Indiana, United States

Parkview Hospital Randallia; 🇺🇸 Fort Wayne, Indiana, United States

Parkview Regional Medical Center; 🇺🇸 Fort Wayne, Indiana, United States

Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

Indiana University/Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

IU Health Methodist Hospital; 🇺🇸 Indianapolis, Indiana, United States

Michiana Hematology Oncology PC-Mishawaka; 🇺🇸 Mishawaka, Indiana, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

McFarland Clinic - Ames; 🇺🇸 Ames, Iowa, United States

IU Health Central Indiana Cancer Centers-East; 🇺🇸 Indianapolis, Indiana, United States

Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

University of Kansas Cancer Center; 🇺🇸 Kansas City, Kansas, United States

The University of Kansas Cancer Center - Olathe; 🇺🇸 Olathe, Kansas, United States

University of Kansas Cancer Center-Overland Park; 🇺🇸 Overland Park, Kansas, United States

Salina Regional Health Center; 🇺🇸 Salina, Kansas, United States

University of Kentucky/Markey Cancer Center; 🇺🇸 Lexington, Kentucky, United States

The James Graham Brown Cancer Center at University of Louisville; 🇺🇸 Louisville, Kentucky, United States

UofL Health Medical Center Northeast; 🇺🇸 Louisville, Kentucky, United States

Tulane University School of Medicine; 🇺🇸 New Orleans, Louisiana, United States

University Medical Center New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Ochsner Medical Center Jefferson; 🇺🇸 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

UM Upper Chesapeake Medical Center; 🇺🇸 Bel Air, Maryland, United States

Central Maryland Radiation Oncology in Howard County; 🇺🇸 Columbia, Maryland, United States

UM Baltimore Washington Medical Center/Tate Cancer Center; 🇺🇸 Glen Burnie, Maryland, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor; 🇺🇸 Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Trinity Health Medical Center - Brighton; 🇺🇸 Brighton, Michigan, United States

University of Michigan - Brighton Center for Specialty Care; 🇺🇸 Brighton, Michigan, United States

Henry Ford Cancer Institute-Downriver; 🇺🇸 Brownstown, Michigan, United States

Henry Ford Macomb Hospital-Clinton Township; 🇺🇸 Clinton Township, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital; 🇺🇸 Grand Rapids, Michigan, United States

Allegiance Health; 🇺🇸 Jackson, Michigan, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

University of Michigan Health - Sparrow Lansing; 🇺🇸 Lansing, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital; 🇺🇸 Livonia, Michigan, United States

Henry Ford Medical Center-Columbus; 🇺🇸 Novi, Michigan, United States

Corewell Health William Beaumont University Hospital; 🇺🇸 Royal Oak, Michigan, United States

MyMichigan Medical Center Saginaw; 🇺🇸 Saginaw, Michigan, United States

Corewell Health Beaumont Troy Hospital; 🇺🇸 Troy, Michigan, United States

Henry Ford West Bloomfield Hospital; 🇺🇸 West Bloomfield, Michigan, United States

University of Michigan Health - West; 🇺🇸 Wyoming, Michigan, United States

Sanford Joe Lueken Cancer Center; 🇺🇸 Bemidji, Minnesota, United States

Minnesota Oncology - Burnsville; 🇺🇸 Burnsville, Minnesota, United States

Miller-Dwan Hospital; 🇺🇸 Duluth, Minnesota, United States

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Coborn Cancer Center at Saint Cloud Hospital; 🇺🇸 Saint Cloud, Minnesota, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Saint Francis Medical Center; 🇺🇸 Cape Girardeau, Missouri, United States

MU Health - University Hospital/Ellis Fischel Cancer Center; 🇺🇸 Columbia, Missouri, United States

Siteman Cancer Center at West County Hospital; 🇺🇸 Creve Coeur, Missouri, United States

North Kansas City Hospital; 🇺🇸 Kansas City, Missouri, United States

The University of Kansas Cancer Center-South; 🇺🇸 Kansas City, Missouri, United States

University of Kansas Cancer Center - North; 🇺🇸 Kansas City, Missouri, United States

University of Kansas Cancer Center - Lee's Summit; 🇺🇸 Lee's Summit, Missouri, United States

Phelps Health Delbert Day Cancer Institute; 🇺🇸 Rolla, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center-South County; 🇺🇸 Saint Louis, Missouri, United States

Missouri Baptist Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Siteman Cancer Center at Saint Peters Hospital; 🇺🇸 Saint Peters, Missouri, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

CHI Health Good Samaritan; 🇺🇸 Kearney, Nebraska, United States

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

Alegent Health Bergan Mercy Medical Center; 🇺🇸 Omaha, Nebraska, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center; 🇺🇸 Lebanon, New Hampshire, United States

Memorial Sloan Kettering Basking Ridge; 🇺🇸 Basking Ridge, New Jersey, United States

The Cancer Institute of New Jersey Hamilton; 🇺🇸 Hamilton, New Jersey, United States

Saint Barnabas Medical Center; 🇺🇸 Livingston, New Jersey, United States

Monmouth Medical Center; 🇺🇸 Long Branch, New Jersey, United States

Memorial Sloan Kettering Monmouth; 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen; 🇺🇸 Montvale, New Jersey, United States

Virtua Memorial; 🇺🇸 Mount Holly, New Jersey, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Rutgers New Jersey Medical School; 🇺🇸 Newark, New Jersey, United States

Sparta Cancer Treatment Center; 🇺🇸 Sparta, New Jersey, United States

Community Medical Center; 🇺🇸 Toms River, New Jersey, United States

Virtua Voorhees; 🇺🇸 Voorhees, New Jersey, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

New Mexico Oncology Hematology Consultants; 🇺🇸 Albuquerque, New Mexico, United States

South Shore University Hospital; 🇺🇸 Bay Shore, New York, United States

Montefiore Medical Center-Einstein Campus; 🇺🇸 Bronx, New York, United States

Montefiore Medical Center - Moses Campus; 🇺🇸 Bronx, New York, United States

New York-Presbyterian/Brooklyn Methodist Hospital; 🇺🇸 Brooklyn, New York, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Sands Cancer Center; 🇺🇸 Canandaigua, New York, United States

Memorial Sloan Kettering Westchester; 🇺🇸 Harrison, New York, United States

Northwell Health/Center for Advanced Medicine; 🇺🇸 Lake Success, New York, United States

NYU Langone Hospital - Long Island; 🇺🇸 Mineola, New York, United States

NYU Langone Hospital - Brooklyn; 🇺🇸 Brooklyn, New York, United States

Arnot Ogden Medical Center/Falck Cancer Center; 🇺🇸 Elmira, New York, United States

Memorial Sloan Kettering Commack; 🇺🇸 Commack, New York, United States

Mount Sinai Union Square; 🇺🇸 New York, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone; 🇺🇸 New York, New York, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Wilmot Cancer Institute Radiation Oncology at Greece; 🇺🇸 Rochester, New York, United States

Highland Hospital; 🇺🇸 Rochester, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Memorial Sloan Kettering Sleepy Hollow; 🇺🇸 Sleepy Hollow, New York, United States

State University of New York Upstate Medical University; 🇺🇸 Syracuse, New York, United States

Memorial Sloan Kettering Nassau; 🇺🇸 Uniondale, New York, United States

Atrium Health Stanly/LCI-Albemarle; 🇺🇸 Albemarle, North Carolina, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

Carolinas Medical Center/Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

Atrium Health Pineville/LCI-Pineville; 🇺🇸 Charlotte, North Carolina, United States

Atrium Health University City/LCI-University; 🇺🇸 Charlotte, North Carolina, United States

Atrium Health Cabarrus/LCI-Concord; 🇺🇸 Concord, North Carolina, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

ECU Health Oncology Kinston; 🇺🇸 Kinston, North Carolina, United States

Atrium Health Union/LCI-Union; 🇺🇸 Monroe, North Carolina, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Sanford Bismarck Medical Center; 🇺🇸 Bismarck, North Dakota, United States

Sanford Roger Maris Cancer Center; 🇺🇸 Fargo, North Dakota, United States

Summa Health System - Akron Campus; 🇺🇸 Akron, Ohio, United States

Cleveland Clinic Akron General; 🇺🇸 Akron, Ohio, United States

UH Seidman Cancer Center at UH Avon Health Center; 🇺🇸 Avon, Ohio, United States

Summa Health System - Barberton Campus; 🇺🇸 Barberton, Ohio, United States

UHHS-Chagrin Highlands Medical Center; 🇺🇸 Beachwood, Ohio, United States

Geauga Hospital; 🇺🇸 Chardon, Ohio, United States

Adena Regional Medical Center; 🇺🇸 Chillicothe, Ohio, United States

University of Cincinnati Cancer Center-UC Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Mercy Cancer Center-Elyria; 🇺🇸 Elyria, Ohio, United States

Cleveland Clinic Cancer Center Independence; 🇺🇸 Independence, Ohio, United States

OhioHealth Mansfield Hospital; 🇺🇸 Mansfield, Ohio, United States

Hillcrest Hospital Cancer Center; 🇺🇸 Mayfield Heights, Ohio, United States

Summa Health Medina Medical Center; 🇺🇸 Medina, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

UH Seidman Cancer Center at Southwest General Hospital; 🇺🇸 Middleburg Heights, Ohio, United States

University Hospitals Parma Medical Center; 🇺🇸 Parma, Ohio, United States

Southern Ohio Medical Center; 🇺🇸 Portsmouth, Ohio, United States

University Hospitals Portage Medical Center; 🇺🇸 Ravenna, Ohio, United States

North Coast Cancer Care; 🇺🇸 Sandusky, Ohio, United States

UH Seidman Cancer Center at Firelands Regional Medical Center; 🇺🇸 Sandusky, Ohio, United States

Cleveland Clinic Cancer Center Strongsville; 🇺🇸 Strongsville, Ohio, United States

University of Cincinnati Cancer Center-West Chester; 🇺🇸 West Chester, Ohio, United States

UHHS-Westlake Medical Center; 🇺🇸 Westlake, Ohio, United States

Cleveland Clinic Wooster Family Health and Surgery Center; 🇺🇸 Wooster, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Clackamas Radiation Oncology Center; 🇺🇸 Clackamas, 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

Carlisle Regional Cancer Center; 🇺🇸 Carlisle, 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

UPMC Pinnacle Cancer Center/Community Osteopathic Campus; 🇺🇸 Harrisburg, Pennsylvania, United States

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, 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

UPMC Cancer Center - Monroeville; 🇺🇸 Monroeville, Pennsylvania, United States

UPMC Hillman Cancer Center in Coraopolis; 🇺🇸 Moon, Pennsylvania, United States

UPMC Cancer Center-Natrona Heights; 🇺🇸 Natrona Heights, Pennsylvania, United States

UPMC Jameson; 🇺🇸 New Castle, Pennsylvania, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Temple University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Magee Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Saint Margaret; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC-Shadyside Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UPMC Jefferson Regional Radiation Oncology; 🇺🇸 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 Uniontown Hospital Radiation Oncology; 🇺🇸 Uniontown, Pennsylvania, United States

UPMC Washington Hospital Radiation Oncology; 🇺🇸 Washington, Pennsylvania, United States

Reading Hospital; 🇺🇸 West Reading, Pennsylvania, United States

Wexford Health and Wellness Pavilion; 🇺🇸 Wexford, Pennsylvania, United States

Prisma Health Cancer Institute - Spartanburg; 🇺🇸 Boiling Springs, South Carolina, United States

Prisma Health Cancer Institute - Faris; 🇺🇸 Greenville, South Carolina, United States

Prisma Health Cancer Institute - Eastside; 🇺🇸 Greenville, South Carolina, United States

AnMed Health Cancer Center; 🇺🇸 Anderson, South Carolina, United States

Saint Joseph's/Candler - Bluffton Campus; 🇺🇸 Bluffton, South Carolina, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Prisma Health Cancer Institute - Greer; 🇺🇸 Greer, South Carolina, United States

Gibbs Cancer Center-Pelham; 🇺🇸 Greer, South Carolina, United States

Rock Hill Radiation Therapy Center; 🇺🇸 Rock Hill, South Carolina, United States

Prisma Health Cancer Institute - Seneca; 🇺🇸 Seneca, South Carolina, United States

Spartanburg Medical Center; 🇺🇸 Spartanburg, South Carolina, United States

Rapid City Regional Hospital; 🇺🇸 Rapid City, South Dakota, United States

Sanford USD Medical Center - Sioux Falls; 🇺🇸 Sioux Falls, South Dakota, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

MD Anderson in The Woodlands; 🇺🇸 Conroe, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas; 🇺🇸 Dallas, Texas, United States

University of Texas Medical Branch; 🇺🇸 Galveston, Texas, United States

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

MD Anderson West Houston; 🇺🇸 Houston, Texas, United States

MD Anderson League City; 🇺🇸 League City, Texas, United States

UTMB Cancer Center at Victory Lakes; 🇺🇸 League City, Texas, United States

Covenant Medical Center-Lakeside; 🇺🇸 Lubbock, Texas, United States

MD Anderson in Sugar Land; 🇺🇸 Sugar Land, Texas, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States

Saint George Regional Medical Center; 🇺🇸 Saint George, Utah, United States

Utah Cancer Specialists-Salt Lake City; 🇺🇸 Salt Lake City, Utah, United States

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Dartmouth Cancer Center - North; 🇺🇸 Saint Johnsbury, Vermont, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

Sentara Cancer Institute at Sentara CarePlex Hospital; 🇺🇸 Hampton, Virginia, United States

Sentara Norfolk General Hospital; 🇺🇸 Norfolk, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Sentara Virginia Beach General Hospital; 🇺🇸 Virginia Beach, Virginia, United States

Saint Francis Hospital; 🇺🇸 Federal Way, Washington, United States

Tri-Cities Cancer Center; 🇺🇸 Kennewick, Washington, United States

PeaceHealth Saint John Medical Center; 🇺🇸 Longview, Washington, United States

Skagit Regional Health Cancer Care Center; 🇺🇸 Mount Vernon, Washington, United States

University of Washington Medical Center - Montlake; 🇺🇸 Seattle, Washington, United States

Spokane Valley Cancer Center-Mayfair; 🇺🇸 Spokane, Washington, United States

Spokane Valley Cancer Center-Mission; 🇺🇸 Spokane, Washington, United States

Wenatchee Valley Hospital and Clinics; 🇺🇸 Wenatchee, Washington, United States

West Virginia University Healthcare; 🇺🇸 Morgantown, West Virginia, United States

Camden Clark Medical Center; 🇺🇸 Parkersburg, West Virginia, United States

Wheeling Hospital/Schiffler Cancer Center; 🇺🇸 Wheeling, West Virginia, United States

Langlade Hospital and Cancer Center; 🇺🇸 Antigo, Wisconsin, United States

Saint Vincent Hospital Cancer Center Green Bay; 🇺🇸 Green Bay, Wisconsin, United States

Froedtert West Bend Hospital/Kraemer Cancer Center; 🇺🇸 West Bend, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Saint Mary's; 🇺🇸 Green Bay, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - Johnson Creek; 🇺🇸 Johnson Creek, Wisconsin, United States

Gundersen Lutheran Medical Center; 🇺🇸 La Crosse, Wisconsin, United States

Mayo Clinic Health System-Franciscan Healthcare; 🇺🇸 La Crosse, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States

Bay Area Medical Center; 🇺🇸 Marinette, Wisconsin, United States

Marshfield Medical Center; 🇺🇸 Marshfield, Wisconsin, United States

Froedtert Menomonee Falls Hospital; 🇺🇸 Menomonee Falls, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Marshfield Medical Center - Minocqua; 🇺🇸 Minocqua, Wisconsin, United States

Cancer Center of Western Wisconsin; 🇺🇸 New Richmond, Wisconsin, United States

Drexel Town Square Health Center; 🇺🇸 Oak Creek, Wisconsin, United States

Aspirus Cancer Care - James Beck Cancer Center; 🇺🇸 Rhinelander, Wisconsin, United States

Aspirus Cancer Care - Stevens Point; 🇺🇸 Stevens Point, Wisconsin, United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay; 🇺🇸 Sturgeon Bay, Wisconsin, United States

Aspirus Regional Cancer Center; 🇺🇸 Wausau, Wisconsin, United States

Aspirus Cancer Care - Wisconsin Rapids; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada

Chinese University of Hong Kong-Prince of Wales Hospital; 🇭🇰 Shatin, Hong Kong