Clinical trial NCT03258554: Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin
Official title: Randomized Phase II/III Trial of Radiotherapy With Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy With Concurrent Cetuximab in Patients With Locoregionally Advanced Head and Neck Cancer With a Contraindication to Cisplatin
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Head and Neck Squamous Cell Carcinoma
Hypopharyngeal Squamous Cell Carcinoma
Laryngeal Squamous Cell Carcinoma
Oral Cavity Squamous Cell Carcinoma
Oropharyngeal Squamous Cell Carcinoma
Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Squamous Cell Carcinoma of Unknown Primary
Stage III Hypopharyngeal Carcinoma AJCC v8
Stage III Laryngeal Cancer AJCC v8
Stage III Lip and Oral Cavity Cancer AJCC v8
Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage IVA Hypopharyngeal Carcinoma AJCC v8
Stage IVA Laryngeal Cancer AJCC v8
Stage IVA Lip and Oral Cavity Cancer AJCC v8
Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Stage IVB Hypopharyngeal Carcinoma AJCC v8
Stage IVB Laryngeal Cancer AJCC v8
Stage IVB Lip and Oral Cavity Cancer AJCC v8
Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Canadian Cancer Trials Group
name: NRG Oncology
First posted: 2017-08-23
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread to a local and/or regional area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. It is not known if radiation therapy with durvalumab will work better than the usual therapy of radiation therapy with cetuximab in treating patients with head and neck cancer.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (MEDI4736 \[durvalumab\]) is safe in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)

SECONDARY OBJECTIVES:

I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.

II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.

III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 \[FDG\]-positron emission tomography \[PET\]-computed tomography \[CT\]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.

IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in the physical function domain of European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally advanced HNC who have a contraindication to cisplatin.

V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT) will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically unfit for cisplatin.

VI. To compare swallowing related performance and function short and long term using the Performance Status Scale for Head \& Neck Cancer Patients (PSS-HN).

VII. To evaluate gastrostomy tube retention rates between arms.

EXPLORATORY OBJECTIVES:

I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.

II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.

III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24 months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI (subscales) between arms in patients with locoregionally advanced HNC who have a contraindication to cisplatin.

IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and PRO-CTCAE.

V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.

VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.

ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA
* Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary prior to step 1 registration; submission of hematoxylin and eosin (H\&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue block (or punch biopsy of FFPE block) to the biospecimen bank at University of California, San Francisco (UCSF) for central review for oropharyngeal and unknown primaries and for p16 analysis for all other non-oropharyngeal primaries is mandatory for all patients; investigators should check with their pathology department regarding release of biospecimens before approaching patients about participation in the trial; for oropharyngeal and unknown primaries, submission of H\&E and p16 stained slides (with the required block for PD-L1) to the biospecimen bank at UCSF for central review is also required prior to step 2 registration

  * Note: fine needle aspirates (FNA) samples are not acceptable since they do not provide enough material for PD-L1 and p16 testing; however, if a cell block derived from the FNA is available, it is allowable if there are sufficient cells present in the block for PD-L1 testing; Dr. Jordan will determine this upon receipt; for sites submitting FNA cell blocks for ALL patients they must do so within 7-10 business days from registering the patient; sites must confirm with their cytology/pathology labs to make sure they can provide the required material as the bank must be able to retain these samples for the mandatory testing
* Patients must have locoregionally advanced head and neck squamous cell carcinoma (HNSCC)

  * For p16-positive oropharyngeal/unknown primaries, American Joint Committee on Cancer \[AJCC\] 8th edition stage III and selected stage I-II based on smoking status in pack-years
  * For laryngeal, hypopharyngeal, and oral cavity primaries and p16-negative oropharyngeal/unknown primaries, AJCC 8th edition stage III-IVB
  * Based on the following minimum diagnostic workup within 60 days prior to step 1 registration:

    * General history and physical examination by a radiation oncologist or medical oncologist or ear, nose and throat (ENT) or head \& neck surgeon
    * For larynx, hypopharynx, and base of tongue primaries, a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is required, unless the patient cannot tolerate or refuses
  * Imaging of the head and neck with a neck CT or magnetic resonance imaging (MRI) (with contrast, unless contraindicated) or PET/CT; note that the CT portion of the PET/CT must be of diagnostic quality, including contrast administration unless contraindicated. If the CT portion of the PET/CT study is low-dose (non-diagnostic), then an additional CT or MRI study with contrast (unless contraindicated) is required
  * Chest imaging: chest CT with and without contrast (unless contraindicated) or PET/CT
* Patients must have a contraindication to cisplatin as defined in the following bullet points; sites must complete the online tool at comogram.org prior to step 1 registration to determine if the patient is eligible; the scores must be recorded on a case report form (CRF)

  * Age \>= 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 30 days prior to step 1 registration:

    * Modified Charlson Comorbidity Index \>= 1
    * Adult Comorbidity Evaluation (ACE)-27 Index \>= 1
    * Generalized Competing Event Model for Cancer Risk (GCE) omega PFS score \< 0.80
    * Geriatric screening (G-8) score =\< 14
    * Cancer and Aging Research Group (CARG) toxicity score \>= 30%
    * Cumulative Illness Rating scale for Geriatrics (CIRS-G) score \>= 4 OR
  * Age \< 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 30 days prior to step 1 registration

    * Modified Charlson Comorbidity Index \>= 1
    * ACE-27 Index \>= 1
    * GCE omega PFS-score \< 0.80
    * G-8 score =\< 14
    * CARG Toxicity score \>= 30%
    * CIRS-G score \>= 4 OR
  * Age \>= 18 with an absolute or relative contraindication to cisplatin, defined as one or more of the following within 30 days prior to step 1 registration:

    * Creatinine clearance (CC) \> 30 and \< 60 cc/min; for this calculation, use the Cockcroft-Gault formula
    * Zubrod performance status 2 prior to step 1 registration
    * Pre-existing peripheral neuropathy grade \>= 1
    * History of hearing loss, defined as either:

      * Existing need of a hearing aid OR
      * \>= 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
* Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (within 14 days prior to step 1 registration)
* Platelets \>= 100,000 cells/mm\^3 (within 14 days prior to step 1 registration)
* Hemoglobin \>= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dl is acceptable) (within 14 days prior to step 1 registration)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 2.5 times institutional upper limit of normal (within 14 days prior to step 1 registration)
* Serum bilirubin =\< 1.5 x institutional upper limit of normal (within 14 days prior to step 1 registration)
* Measured creatinine clearance (CL) \> 30 mL/min or calculated creatinine CL \> 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (within 14 days prior to step 1 registration)
* For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration; Note: women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:

  * Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
  * Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
* The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
* PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA
* For patients with oropharyngeal or unknown primaries: p16 determination by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review

  * Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries, analysis of p16 status prior to step 2 registration/randomization is not required (p16 status will be analyzed centrally post-hoc); step 2 registration for these patients can be completed after step 1 registration

Exclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA
* Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer); synchronous head and neck primaries are ineligible
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

  * Note: Prior external beam radiotherapy is excluded, but iodine 131 is allowed
* Prior immunotherapy
* Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
* Major surgery within 28 days prior to step 1 registration
* Proven evidence of distant metastases
* If both of the following conditions are present, the patient is ineligible:

  * =\< 10 pack-year smoking history
  * p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1 (AJCC 8th Edition)

    * Note: in the event that a registered patient with =\< 10 pack-years has a p16-positive result on central review with the tumor and nodal stage T0-3, N0-1 (AJCC 8th Edition), then the site will be notified that the patient is ineligible
* Zubrod performance status \>= 3
* Body weight =\< 30 kg
* Patients with oral cavity cancer are excluded from participation if the patient is medically operable and resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist;(please consult the surgical oncology co-principal investigator \[PI\], Steven Chang, Doctor of Medicine \[MD\], if clarification is needed on an individual case)
* Sodium \< 130 mmol/L or \> 155 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
* Potassium \< 3.5 mmol/L or \> 6 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
* Fasting glucose \< 40 mg/dl or \> 400 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
* Serum calcium (ionized or adjusted for albumin) \< 7 mg/dl or \> 12.5 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
* Magnesium \< 0.9 mg/dl or \> 3 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
* Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to step 1 registration
* Transmural myocardial infarction within 3 months prior to step 1 registration
* Respiratory illness requiring hospitalization at the time of step 1 registration

  * Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial
* 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 step 1 registration
* History of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Clinically apparent jaundice and/or known coagulation defects
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)

  * The following are exceptions to this criterion:

    * Patients with vitiligo or alopecia;
    * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
    * Any chronic skin condition that does not require systemic therapy;
    * Patients without active disease in the last 5 years may be included but only after consultation with the medical oncology study chair;
    * Patients with celiac disease controlled by diet alone
* History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease 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 treatment involved in this protocol may be immunosuppressive; patients with known HIV, CD4 counts \>= 200/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included
* Current or prior use of immunosuppressive medication within 14 days before step 1 registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
* Receipt of live attenuated vaccination within 30 days prior to step 1 registration
* Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic; women who are breastfeeding are also excluded
* Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or any of study drug excipients
* History of allogenic organ transplantation
* Uncontrolled hypertension
* Uncontrolled cardiac arrhythmia
* Uncontrolled serious chronic gastrointestinal condition associated with diarrhea
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), hepatitis B (known positive hepatitis B virus \[HBV\] surface antigen \[HBsAg\] result), hepatitis C; patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus \[HCV\]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase]
timeFrame: From start of durvalumab to 4 weeks after radiation therapy, approximately 13 weeks. Weekly during RT, at RT end, prior to adjuvant durvalumab, one month after end of RT.
measure: Progression-free Survival (Percentage of Participants Alive Without Progression) [Phase II Primary]
timeFrame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
measure: Overall Survival (Percentage of Participants Alive) [Originally Phase III Primary / Now Phase II Secondary]
timeFrame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Secondary outcomes:
measure: Locoregional Failure (Percentage of Participants With Locoregional Failure)
timeFrame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
measure: Distant Metastasis (Percentage of Participants With Distant Metastasis)
timeFrame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
measure: Competing Mortality (Percentage of Participants Who Died Due to Causes Other Than Study Cancer)
timeFrame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
measure: Percentage of Participants With Complete or Partial Response at 4-month Scan Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1
timeFrame: Baseline and 4 months after end of RT (approximately 6.5 months)
measure: Number of Participants by Highest Grade Adverse Event Reported
timeFrame: From randomization to last follow-up: weekly during RT, RT end, from end of RT: months 1, (Cetuximab: 2, 3,) 4, 8, 12, 18, 24, 30, 36, then annually. Additionally, prior to each adjuvant durvalumab cycle. Maximum follow-up at time of analysis= 4.2 yr.
measure: Change in Quality of Life (QOL) Analysis
timeFrame: Baseline up to 12 months
measure: Change in Swallowing QOL Using Total Composite M. D. Anderson Dysphagia Inventory (MDADI) Score
timeFrame: Baseline up to 1 year
measure: Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline PD-L1 (Programmed Cell Death Ligand 1) Expression
timeFrame: From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
measure: Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline p16 Status
timeFrame: From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
Other outcomes:
measure: Secondary Biomarker Analysis
timeFrame: Baseline up to 4 months after RT
measure: Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to 3 years
measure: QOL Endpoints Using Other Items in EORTC QLQ/HN35, EQ5D and MDADI Subscales
timeFrame: Up to 12-24 months from end of RT
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Goodyear
country: United States
facility: CTCA at Western Regional Medical Center
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center-North Campus
state: Arizona
city: Antioch
country: United States
facility: Kaiser Permanente-Deer Valley Medical Center
state: California
city: Auburn
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Auburn
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Dublin
country: United States
facility: Kaiser Permanente Dublin
state: California
city: Fremont
country: United States
facility: Kaiser Permanente-Fremont
state: California
city: Fresno
country: United States
facility: Fresno Cancer Center
state: California
city: Fresno
country: United States
facility: Kaiser Permanente-Fresno
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Modesto
country: United States
facility: Kaiser Permanente-Modesto
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland-Broadway
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Rancho Cordova
country: United States
facility: Kaiser Permanente-Rancho Cordova Cancer Center
state: California
city: Richmond
country: United States
facility: Kaiser Permanente-Richmond
state: California
city: Rohnert Park
country: United States
facility: Rohnert Park Cancer Center
state: California
city: Roseville
country: United States
facility: Kaiser Permanente-Roseville
state: California
city: Roseville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Roseville
state: California
city: Roseville
country: United States
facility: The Permanente Medical Group-Roseville Radiation Oncology
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Downtown Commons
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente-South Sacramento
state: California
city: Sacramento
country: United States
facility: South Sacramento Cancer Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente-San Francisco
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: San Jose
country: United States
facility: Kaiser Permanente-Santa Teresa-San Jose
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente San Leandro
state: California
city: San Rafael
country: United States
facility: Kaiser San Rafael-Gallinas
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente-Santa Rosa
state: California
city: South Pasadena
country: United States
facility: City of Hope South Pasadena
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente Cancer Treatment Center
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente-South San Francisco
state: California
city: Stockton
country: United States
facility: Kaiser Permanente-Stockton
state: California
city: Torrance
country: United States
facility: Torrance Memorial Physician Network - Cancer Care
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Truckee
country: United States
facility: Gene Upshaw Memorial Tahoe Forest Cancer Center
state: California
city: Vacaville
country: United States
facility: Kaiser Permanente Medical Center-Vacaville
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente-Vallejo
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente-Walnut Creek
state: California
city: Aurora
country: United States
facility: UCHealth University of Colorado Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Colorado Springs
country: United States
facility: UCHealth Memorial Hospital Central
state: Colorado
city: Colorado Springs
country: United States
facility: Memorial Hospital North
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Loveland
country: United States
facility: Banner McKee Medical Center
state: Colorado
city: Hamden
country: United States
facility: Smilow Cancer Hospital-Hamden Care Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Trumbull
country: United States
facility: Smilow Cancer Hospital Care Center-Trumbull
state: Connecticut
city: Waterford
country: United States
facility: Smilow Cancer Hospital Care Center - Waterford
state: Connecticut
city: Millville
country: United States
facility: Beebe South Coastal Health Campus
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Coral Gables
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Coral Gables
state: Florida
city: Deerfield Beach
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Deerfield Beach
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc - Waterfront Plaza
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Caldwell
country: United States
facility: Saint Alphonsus Cancer Care Center-Caldwell
state: Idaho
city: Nampa
country: United States
facility: Saint Alphonsus Cancer Care Center-Nampa
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Galesburg
country: United States
facility: Western Illinois Cancer Treatment Center
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Carmel
country: United States
facility: IU Health North Hospital
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital Randallia
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Sidney and Lois Eskenazi Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center East
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center South
state: Indiana
city: Indianapolis
country: United States
facility: Community Cancer Center North
state: Indiana
city: Clive
country: United States
facility: Mercy Cancer Center-West Lakes
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center-Overland Park
state: Kansas
city: Salina
country: United States
facility: Salina Regional Health Center
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Hospital-Westwood Cancer Center
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi Hospitals Wichita
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital Pavilion and Medical Campus
state: Kentucky
city: Louisville
country: United States
facility: The James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Louisville
country: United States
facility: Norton Brownsboro Hospital and Medical Campus
state: Kentucky
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Trinity Health Saint Joseph Mercy Hospital Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Bay City
country: United States
facility: McLaren Cancer Institute-Bay City
state: Michigan
city: Brighton
country: United States
facility: Trinity Health Medical Center - Brighton
state: Michigan
city: Brownstown
country: United States
facility: Henry Ford Cancer Institute-Downriver
state: Michigan
city: Canton
country: United States
facility: Trinity Health Medical Center - Canton
state: Michigan
city: Chelsea
country: United States
facility: Chelsea Hospital
state: Michigan
city: Clarkston
country: United States
facility: McLaren Cancer Institute-Clarkston
state: Michigan
city: Clinton Township
country: United States
facility: Henry Ford Macomb Hospital-Clinton Township
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Weisberg Cancer Treatment Center
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute-Flint
state: Michigan
city: Flint
country: United States
facility: Singh and Arora Hematology Oncology PC
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Karmanos Cancer Institute at McLaren Greater Lansing
state: Michigan
city: Lansing
country: United States
facility: Mid-Michigan Physicians-Lansing
state: Michigan
city: Lansing
country: United States
facility: University of Michigan Health - Sparrow Lansing
state: Michigan
city: Lapeer
country: United States
facility: McLaren Cancer Institute-Lapeer Region
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Cancer Institute-Macomb
state: Michigan
city: Petoskey
country: United States
facility: McLaren Cancer Institute-Northern Michigan
state: Michigan
city: Port Huron
country: United States
facility: McLaren-Port Huron
state: Michigan
city: Saginaw
country: United States
facility: MyMichigan Medical Center Saginaw
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Bemidji
country: United States
facility: Sanford Joe Lueken Cancer Center
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center at Saint Cloud Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center at Saint Peters Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Kalispell
country: United States
facility: Logan Health Medical Center
state: Montana
city: Grand Island
country: United States
facility: Nebraska Cancer Specialists/Oncology Hematology West PC
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Bronx
country: United States
facility: James J Peters VA Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Albemarle
country: United States
facility: Atrium Health Stanly/LCI-Albemarle
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health Pineville/LCI-Pineville
state: North Carolina
city: Concord
country: United States
facility: Atrium Health Cabarrus/LCI-Concord
state: North Carolina
city: Hendersonville
country: United States
facility: Margaret R Pardee Memorial Hospital
state: North Carolina
city: Monroe
country: United States
facility: Atrium Health Union/LCI-Union
state: North Carolina
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Canton
country: United States
facility: Cleveland Clinic Mercy Hospital
state: Ohio
city: Canton
country: United States
facility: Aultman Health Foundation
state: Ohio
city: Chardon
country: United States
facility: Geauga Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Mansfield
country: United States
facility: Cleveland Clinic Cancer Center Mansfield
state: Ohio
city: Mentor
country: United States
facility: UH Seidman Cancer Center at Lake Health Mentor Campus
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Westlake
country: United States
facility: UHHS-Westlake Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic Wooster Family Health and Surgery Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Corvallis
country: United States
facility: Good Samaritan Hospital
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: Abington
country: United States
facility: Jefferson Abington Hospital
state: Pennsylvania
city: Broomall
country: United States
facility: Crozer-Keystone Regional Cancer Center at Broomall
state: Pennsylvania
city: Chadds Ford
country: United States
facility: Christiana Care Health System-Concord Health Center
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Lewisburg
country: United States
facility: Geisinger Medical Oncology-Lewisburg
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Monroeville
country: United States
facility: Forbes Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC-Shadyside Hospital
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Group PC-Robert Packer Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Wexford
country: United States
facility: Wexford Health and Wellness Pavilion
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Willow Grove
country: United States
facility: Asplundh Cancer Pavilion
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greer
country: United States
facility: Gibbs Cancer Center-Pelham
state: South Carolina
city: Rock Hill
country: United States
facility: Rock Hill Radiation Therapy Center
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Saint Johnsbury
country: United States
facility: Dartmouth Cancer Center - North
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: VCU Massey Cancer Center at Stony Point
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Saint Mary's
state: Wisconsin
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Johnson Creek
country: United States
facility: University of Wisconsin Carbone Cancer Center - Johnson Creek
state: Wisconsin
city: Kenosha
country: United States
facility: Aurora Cancer Care-Kenosha South
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
city: Marinette
country: United States
facility: Aurora Bay Area Medical Group-Marinette
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Froedtert Menomonee Falls Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Zablocki Veterans Administration Medical Center
state: Wisconsin
city: Mukwonago
country: United States
facility: ProHealth D N Greenwald Center
state: Wisconsin
city: Oconomowoc
country: United States
facility: ProHealth Oconomowoc Memorial Hospital
state: Wisconsin
city: Sheboygan
country: United States
facility: Vince Lombardi Cancer Clinic-Sheboygan
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: West Allis
country: United States
facility: Aurora West Allis Medical Center
state: Wisconsin
city: West Bend
country: United States
facility: Froedtert West Bend Hospital/Kraemer Cancer Center
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre (MUHC)
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: NRG Oncology
name: Loren K Mell
role: PRINCIPAL_INVESTIGATOR
References: