Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Suspended
CT.gov ID
NCT03258554
Collaborator
Canadian Cancer Trials Group (Other), NRG Oncology (Other)
493
256
2
96.6
1.9
0

Study Details

Study Description

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:
  1. 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:
  1. 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.

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

  3. 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.

  4. 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.

  5. 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.

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

  7. To evaluate gastrostomy tube retention rates between arms.

EXPLORATORY OBJECTIVES:
  1. 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.

  2. 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.

  3. 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.

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

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

  6. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
493 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 12, 2017
Anticipated Primary Completion Date :
Dec 31, 2025
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I (cetuximab, radiation therapy)

Patients receive cetuximab 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 IMRT 5 fractions per week for up to 7 weeks.

Biological: Cetuximab
Given IV
Other Names:
  • Cetuximab Biosimilar CDP-1
  • Cetuximab Biosimilar CMAB009
  • Cetuximab Biosimilar KL 140
  • Chimeric Anti-EGFR Monoclonal Antibody
  • Chimeric MoAb C225
  • Chimeric Monoclonal Antibody C225
  • Erbitux
  • IMC-C225
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Quality-of-Life Assessment
    Ancillary studies
    Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Experimental: Arm II (durvalumab, radiation therapy)

    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.

    Biological: Durvalumab
    Given IV
    Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Quality-of-Life Assessment
    Ancillary studies
    Other Names:
  • Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies

    Outcome Measures

    Primary Outcome Measures

    1. Dose-limiting toxicity (DLT) defined as the occurrence of an adverse event (AE) during the specified observation window (Lead -in) [Up to 4 weeks after radiation therapy (RT)]

      AEs will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    2. Progression-free survival (PFS) (Phase II) [From randomization until first evidence of local, regional, or distant disease progression or recurrence, or death from any cause, assessed up to 3 years]

      PFS will be estimated using the Kaplan-Meier method. The difference in PFS between the two arms will be tested using a log-rank test.

    3. Overall survival (OS) (Phase III) [From randomization until death from any cause, assessed up to 3 years]

      OS will be estimated using the Kaplan-Meier method. The difference in OS between the two arms will be tested using a log-rank test. Exploratory analysis adjusting for important factors such as age, site, Zubrod performance status, and clinical stages will be conducted using Cox models.

    Secondary Outcome Measures

    1. Locoregional failure (LRF) [From randomization until first evidence of local, regional disease progression or recurrence, or death from study cancer or unknown causes, assessed up to 3 years]

      LRF will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.

    2. Distant metastasis (DM) [From randomization until first evidence of distant metastasis, assessed up to 3 years]

      DM will be estimated by cumulative incidence methods and compared using a cause-specific log-rank test. All failure times will be measured from the date of study randomization to the date of failure or last follow up.

    3. Competing mortality [Up to 3 years]

      Will be estimated by cumulative incidence methods and the effects of other covariates will be assessed using the Generalized Competing Event Model for Cancer Risk model.

    4. Response on 4-month fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) [Up to 4 months]

      Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST). Response rates between the two arms will be compared using Fisher's exact test.

    5. Acute toxicity [Up to 180 days after the end of radiation therapy]

      The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.

    6. Late toxicity [Up to 3 years]

      Late toxicities > 180 days after the end of radiation therapy. The rates of adverse events will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.

    7. Change in quality of life (QOL) analysis [Baseline up to 12 months]

      Assessed using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ)/Head-and-Neck module (H&N35), EuroQol- 5 Dimension (EQ5D), M. D. Anderson Dysphagia Inventory (MDADI), patient reported outcomes (PRO)-CTCAE, geriatric screening (G8). The mean summary score of the EORTC QLQ/H&N35, EQ5D, MDADI, PRO-CTCAE, G8, CCI, and the subscales will be determined. The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.

    8. Change in swallowing QOL using total composite M. D. Anderson Dysphagia Inventory (MDADI) score [Baseline up to 1 year]

      The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis.

    9. Translational research, including PD-L1 and p16 [Up to 3 years]

      Analyses of interaction between treatment arm and marker status will be done. Additionally toxicity for the two arms by marker status will be compared. Univariable and multivariable analysis will be performed using the Cox proportional hazards model for OS. Potential covariates evaluated for the multivariate models would be assigned treatment, age, Zubrod performance status, T-stage, N-stage, primary site, smoking history, other risk factors, as well as p16 and/PD-L1.

    Other Outcome Measures

    1. Secondary biomarker analysis [Baseline up to 4 months after RT]

      Will perform multiparametric flow cytometry on peripheral mononuclear cells (PBMC) from patient-derived blood samples to quantify changes in immune cell frequency and activation status before, during and after radiation combined with cetuximab or radiation combined with durvalumab. To assess the statistical significance of pre- to post-treatment changes in levels of immunoglobulin (Ig)Gs as well as other markers, normalized signal intensities (log2) will be tested using a paired t test within an arm and two sample t test between the two arms. If the distribution assumption is violated for the t tests, nonparametric tests, such as the Wilcoxon signed-rank test will be considered. Lastly, the association between PFS and OS and post-treatment changes in frequency and activation state of T-cells, clonality and diversity of T cell receptor (TCR), and IgG levels will be evaluated using a two-sided Wald test at 0.05 level on the basis of Cox models.

    2. Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Up to 3 years]

      PRO-CTCAE is not intended for expedited reporting, real time review or safety reporting. PRO-CTCAE data are exploratory and not currently intended for use in data safety monitoring or adverse event stopping rules.

    3. QOL endpoints using other items in EORTC QLQ/HN35, EQ5D and MDADI subscales [Up to 12-24 months from end of RT]

      The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 University of South Alabama Mitchell Cancer Institute Mobile Alabama United States 36688
    3 Banner MD Anderson Cancer Center Gilbert Arizona United States 85234
    4 CTCA at Western Regional Medical Center Goodyear Arizona United States 85338
    5 Banner University Medical Center - Tucson Tucson Arizona United States 85719
    6 University of Arizona Cancer Center-North Campus Tucson Arizona United States 85719
    7 Kaiser Permanente-Deer Valley Medical Center Antioch California United States 94531
    8 Sutter Cancer Centers Radiation Oncology Services-Auburn Auburn California United States 95603
    9 Alta Bates Summit Medical Center-Herrick Campus Berkeley California United States 94704
    10 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    11 Kaiser Permanente Dublin Dublin California United States 94568
    12 Kaiser Permanente-Fremont Fremont California United States 94538
    13 Fresno Cancer Center Fresno California United States 93720
    14 Kaiser Permanente-Fresno Fresno California United States 93720
    15 UC San Diego Moores Cancer Center La Jolla California United States 92093
    16 Cedars Sinai Medical Center Los Angeles California United States 90048
    17 Kaiser Permanente-Modesto Modesto California United States 95356
    18 Kaiser Permanente Oakland-Broadway Oakland California United States 94611
    19 Kaiser Permanente-Oakland Oakland California United States 94611
    20 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    21 VA Palo Alto Health Care System Palo Alto California United States 94304
    22 Kaiser Permanente-Rancho Cordova Cancer Center Rancho Cordova California United States 95670
    23 Kaiser Permanente-Richmond Richmond California United States 94801
    24 Rohnert Park Cancer Center Rohnert Park California United States 94928
    25 Kaiser Permanente-Roseville Roseville California United States 95661
    26 Sutter Cancer Centers Radiation Oncology Services-Roseville Roseville California United States 95661
    27 The Permanente Medical Group-Roseville Radiation Oncology Roseville California United States 95678
    28 Kaiser Permanente Downtown Commons Sacramento California United States 95814
    29 Sutter Medical Center Sacramento Sacramento California United States 95816
    30 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    31 Kaiser Permanente-South Sacramento Sacramento California United States 95823
    32 South Sacramento Cancer Center Sacramento California United States 95823
    33 Kaiser Permanente-San Francisco San Francisco California United States 94115
    34 UCSF Medical Center-Mount Zion San Francisco California United States 94115
    35 UCSF Medical Center-Mission Bay San Francisco California United States 94158
    36 Kaiser Permanente-Santa Teresa-San Jose San Jose California United States 95119
    37 Kaiser Permanente San Leandro San Leandro California United States 94577
    38 Kaiser San Rafael-Gallinas San Rafael California United States 94903
    39 Kaiser Permanente Medical Center - Santa Clara Santa Clara California United States 95051
    40 Kaiser Permanente-Santa Rosa Santa Rosa California United States 95403
    41 City of Hope South Pasadena South Pasadena California United States 91030
    42 Kaiser Permanente Cancer Treatment Center South San Francisco California United States 94080
    43 Kaiser Permanente-South San Francisco South San Francisco California United States 94080
    44 Kaiser Permanente-Stockton Stockton California United States 95210
    45 Torrance Memorial Physician Network - Cancer Care Torrance California United States 90505
    46 Torrance Memorial Medical Center Torrance California United States 90509
    47 Gene Upshaw Memorial Tahoe Forest Cancer Center Truckee California United States 96161
    48 Kaiser Permanente Medical Center-Vacaville Vacaville California United States 95688
    49 Kaiser Permanente-Vallejo Vallejo California United States 94589
    50 Kaiser Permanente-Walnut Creek Walnut Creek California United States 94596
    51 University of Colorado Hospital Aurora Colorado United States 80045
    52 Penrose-Saint Francis Healthcare Colorado Springs Colorado United States 80907
    53 UCHealth Memorial Hospital Central Colorado Springs Colorado United States 80909
    54 Memorial Hospital North Colorado Springs Colorado United States 80920
    55 Poudre Valley Hospital Fort Collins Colorado United States 80524
    56 McKee Medical Center Loveland Colorado United States 80539
    57 Smilow Cancer Hospital-Hamden Care Center Hamden Connecticut United States 06518
    58 Yale University New Haven Connecticut United States 06520
    59 Smilow Cancer Hospital Care Center-Trumbull Trumbull Connecticut United States 06611
    60 Smilow Cancer Hospital Care Center - Waterford Waterford Connecticut United States 06385
    61 Beebe South Coastal Health Campus Frankford Delaware United States 19945
    62 Helen F Graham Cancer Center Newark Delaware United States 19713
    63 Beebe Health Campus Rehoboth Beach Delaware United States 19971
    64 UM Sylvester Comprehensive Cancer Center at Coral Gables Coral Gables Florida United States 33146
    65 UM Sylvester Comprehensive Cancer Center at Deerfield Beach Deerfield Beach Florida United States 33442
    66 Baptist MD Anderson Cancer Center Jacksonville Florida United States 32207
    67 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    68 Moffitt Cancer Center Tampa Florida United States 33612
    69 Grady Health System Atlanta Georgia United States 30303
    70 Emory University Hospital Midtown Atlanta Georgia United States 30308
    71 Emory University Hospital/Winship Cancer Institute Atlanta Georgia United States 30322
    72 Augusta University Medical Center Augusta Georgia United States 30912
    73 Hawaii Cancer Care Inc - Waterfront Plaza Honolulu Hawaii United States 96813
    74 Queen's Medical Center Honolulu Hawaii United States 96813
    75 The Cancer Center of Hawaii-Liliha Honolulu Hawaii United States 96817
    76 Saint Alphonsus Cancer Care Center-Caldwell Caldwell Idaho United States 83605
    77 Saint Alphonsus Medical Center-Nampa Nampa Idaho United States 83686
    78 Northwestern University Chicago Illinois United States 60611
    79 John H Stroger Jr Hospital of Cook County Chicago Illinois United States 60612
    80 Rush University Medical Center Chicago Illinois United States 60612
    81 University of Illinois Chicago Illinois United States 60612
    82 Decatur Memorial Hospital Decatur Illinois United States 62526
    83 Crossroads Cancer Center Effingham Illinois United States 62401
    84 Western Illinois Cancer Treatment Center Galesburg Illinois United States 61401
    85 Methodist Medical Center of Illinois Peoria Illinois United States 61636
    86 OSF Saint Francis Medical Center Peoria Illinois United States 61637
    87 Memorial Medical Center Springfield Illinois United States 62781
    88 Carle Cancer Center Urbana Illinois United States 61801
    89 IU Health North Hospital Carmel Indiana United States 46032
    90 Parkview Hospital Randallia Fort Wayne Indiana United States 46805
    91 Parkview Regional Medical Center Fort Wayne Indiana United States 46845
    92 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    93 Sidney and Lois Eskenazi Hospital Indianapolis Indiana United States 46202
    94 Community Cancer Center East Indianapolis Indiana United States 46219
    95 Community Cancer Center South Indianapolis Indiana United States 46227
    96 Community Cancer Center North Indianapolis Indiana United States 46256
    97 Mercy Cancer Center-West Lakes Clive Iowa United States 50325
    98 Iowa Methodist Medical Center Des Moines Iowa United States 50309
    99 Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    100 University of Kansas Cancer Center Kansas City Kansas United States 66160
    101 University of Kansas Cancer Center-Overland Park Overland Park Kansas United States 66210
    102 Salina Regional Health Center Salina Kansas United States 67401
    103 University of Kansas Hospital-Westwood Cancer Center Westwood Kansas United States 66205
    104 Ascension Via Christi Hospitals Wichita Wichita Kansas United States 67214
    105 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    106 Norton Hospital Pavilion and Medical Campus Louisville Kentucky United States 40202
    107 The James Graham Brown Cancer Center at University of Louisville Louisville Kentucky United States 40202
    108 Norton Brownsboro Hospital and Medical Campus Louisville Kentucky United States 40241
    109 East Jefferson General Hospital Metairie Louisiana United States 70006
    110 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    111 Boston Medical Center Boston Massachusetts United States 02118
    112 Lahey Hospital and Medical Center Burlington Massachusetts United States 01805
    113 Saint Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    114 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    115 McLaren Cancer Institute-Bay City Bay City Michigan United States 48706
    116 Saint Joseph Mercy Brighton Brighton Michigan United States 48114
    117 Henry Ford Cancer Institute-Downriver Brownstown Michigan United States 48183
    118 Saint Joseph Mercy Canton Canton Michigan United States 48188
    119 Saint Joseph Mercy Chelsea Chelsea Michigan United States 48118
    120 McLaren Cancer Institute-Clarkston Clarkston Michigan United States 48346
    121 Henry Ford Macomb Hospital-Clinton Township Clinton Township Michigan United States 48038
    122 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    123 Henry Ford Hospital Detroit Michigan United States 48202
    124 Weisberg Cancer Treatment Center Farmington Hills Michigan United States 48334
    125 McLaren Cancer Institute-Flint Flint Michigan United States 48532
    126 Singh and Arora Hematology Oncology PC Flint Michigan United States 48532
    127 Allegiance Health Jackson Michigan United States 49201
    128 Karmanos Cancer Institute at McLaren Greater Lansing Lansing Michigan United States 48910
    129 Mid-Michigan Physicians-Lansing Lansing Michigan United States 48912
    130 Sparrow Hospital Lansing Michigan United States 48912
    131 McLaren Cancer Institute-Lapeer Region Lapeer Michigan United States 48446
    132 McLaren Cancer Institute-Macomb Mount Clemens Michigan United States 48043
    133 McLaren Cancer Institute-Northern Michigan Petoskey Michigan United States 49770
    134 McLaren-Port Huron Port Huron Michigan United States 48060
    135 Ascension Saint Mary's Hospital Saginaw Michigan United States 48601
    136 Henry Ford West Bloomfield Hospital West Bloomfield Michigan United States 48322
    137 Sanford Joe Lueken Cancer Center Bemidji Minnesota United States 56601
    138 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    139 Miller-Dwan Hospital Duluth Minnesota United States 55805
    140 Fairview Southdale Hospital Edina Minnesota United States 55435
    141 Unity Hospital Fridley Minnesota United States 55432
    142 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    143 Mayo Clinic in Rochester Rochester Minnesota United States 55905
    144 Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota United States 56303
    145 Regions Hospital Saint Paul Minnesota United States 55101
    146 Saint Francis Medical Center Cape Girardeau Missouri United States 63703
    147 Siteman Cancer Center at West County Hospital Creve Coeur Missouri United States 63141
    148 Washington University School of Medicine Saint Louis Missouri United States 63110
    149 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    150 Siteman Cancer Center at Saint Peters Hospital Saint Peters Missouri United States 63376
    151 Billings Clinic Cancer Center Billings Montana United States 59101
    152 Kalispell Regional Medical Center Kalispell Montana United States 59901
    153 CHI Health Saint Francis Grand Island Nebraska United States 68803
    154 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    155 Memorial Sloan Kettering Basking Ridge Basking Ridge New Jersey United States 07920
    156 Hackensack University Medical Center Hackensack New Jersey United States 07601
    157 Memorial Sloan Kettering Monmouth Middletown New Jersey United States 07748
    158 Memorial Sloan Kettering Bergen Montvale New Jersey United States 07645
    159 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    160 New Mexico Oncology Hematology Consultants Albuquerque New Mexico United States 87109
    161 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    162 James J Peters VA Medical Center Bronx New York United States 10468
    163 Roswell Park Cancer Institute Buffalo New York United States 14263
    164 Memorial Sloan Kettering Commack Commack New York United States 11725
    165 Memorial Sloan Kettering Westchester Harrison New York United States 10604
    166 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    167 NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    168 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    169 University of Rochester Rochester New York United States 14642
    170 Stony Brook University Medical Center Stony Brook New York United States 11794
    171 State University of New York Upstate Medical University Syracuse New York United States 13210
    172 Memorial Sloan Kettering Nassau Uniondale New York United States 11553
    173 Atrium Health Stanly/LCI-Albemarle Albemarle North Carolina United States 28002
    174 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    175 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    176 Atrium Health Pineville/LCI-Pineville Charlotte North Carolina United States 28210
    177 Atrium Health Cabarrus/LCI-Concord Concord North Carolina United States 28025
    178 Margaret R Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    179 Atrium Health Union/LCI-Union Monroe North Carolina United States 28112
    180 Sanford Roger Maris Cancer Center Fargo North Dakota United States 58122
    181 Cleveland Clinic Mercy Hospital Canton Ohio United States 44708
    182 Aultman Health Foundation Canton Ohio United States 44710
    183 Geauga Hospital Chardon Ohio United States 44024
    184 University of Cincinnati Cancer Center-UC Medical Center Cincinnati Ohio United States 45219
    185 Case Western Reserve University Cleveland Ohio United States 44106
    186 MetroHealth Medical Center Cleveland Ohio United States 44109
    187 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    188 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    189 Cleveland Clinic Cancer Center Mansfield Mansfield Ohio United States 44906
    190 UH Seidman Cancer Center at Lake Health Mentor Campus Mentor Ohio United States 44060
    191 North Coast Cancer Care Sandusky Ohio United States 44870
    192 ProMedica Flower Hospital Sylvania Ohio United States 43560
    193 University of Cincinnati Cancer Center-West Chester West Chester Ohio United States 45069
    194 UHHS-Westlake Medical Center Westlake Ohio United States 44145
    195 Cleveland Clinic Wooster Family Health and Surgery Center Wooster Ohio United States 44691
    196 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    197 Good Samaritan Hospital Corvallis Oregon United States 97330
    198 Providence Portland Medical Center Portland Oregon United States 97213
    199 Providence Saint Vincent Medical Center Portland Oregon United States 97225
    200 Kaiser Permanente Northwest Portland Oregon United States 97227
    201 Jefferson Abington Hospital Abington Pennsylvania United States 19001
    202 Crozer-Keystone Regional Cancer Center at Broomall Broomall Pennsylvania United States 19008
    203 Christiana Care Health System-Concord Health Center Chadds Ford Pennsylvania United States 19317
    204 Geisinger Medical Center Danville Pennsylvania United States 17822
    205 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    206 Geisinger Medical Oncology-Lewisburg Lewisburg Pennsylvania United States 17837
    207 Lewistown Hospital Lewistown Pennsylvania United States 17044
    208 Forbes Hospital Monroeville Pennsylvania United States 15146
    209 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    210 Temple University Hospital Philadelphia Pennsylvania United States 19140
    211 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    212 UPMC-Shadyside Hospital Pittsburgh Pennsylvania United States 15232
    213 Guthrie Medical Group PC-Robert Packer Hospital Sayre Pennsylvania United States 18840
    214 Reading Hospital West Reading Pennsylvania United States 19611
    215 Wexford Health and Wellness Pavilion Wexford Pennsylvania United States 15090
    216 Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania United States 18711
    217 Asplundh Cancer Pavilion Willow Grove Pennsylvania United States 19090
    218 Medical University of South Carolina Charleston South Carolina United States 29425
    219 Gibbs Cancer Center-Pelham Greer South Carolina United States 29651
    220 Rock Hill Radiation Therapy Center Rock Hill South Carolina United States 29730
    221 Spartanburg Medical Center Spartanburg South Carolina United States 29303
    222 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    223 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    224 M D Anderson Cancer Center Houston Texas United States 77030
    225 Norris Cotton Cancer Center-North Saint Johnsbury Vermont United States 05819
    226 University of Virginia Cancer Center Charlottesville Virginia United States 22908
    227 Sentara Norfolk General Hospital Norfolk Virginia United States 23507
    228 VCU Massey Cancer Center at Stony Point Richmond Virginia United States 23235
    229 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    230 University of Washington Medical Center - Montlake Seattle Washington United States 98195
    231 West Virginia University Healthcare Morgantown West Virginia United States 26506
    232 Langlade Hospital and Cancer Center Antigo Wisconsin United States 54409
    233 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    234 Saint Vincent Hospital Cancer Center at Saint Mary's Green Bay Wisconsin United States 54303
    235 Aurora BayCare Medical Center Green Bay Wisconsin United States 54311
    236 UW Cancer Center Johnson Creek Johnson Creek Wisconsin United States 53038
    237 Aurora Cancer Care-Kenosha South Kenosha Wisconsin United States 53142
    238 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
    239 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792
    240 Aurora Bay Area Medical Group-Marinette Marinette Wisconsin United States 54143
    241 Froedtert Menomonee Falls Hospital Menomonee Falls Wisconsin United States 53051
    242 Aurora Saint Luke's Medical Center Milwaukee Wisconsin United States 53215
    243 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    244 Zablocki Veterans Administration Medical Center Milwaukee Wisconsin United States 53295
    245 ProHealth D N Greenwald Center Mukwonago Wisconsin United States 53149
    246 ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    247 Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin United States 53081
    248 Aurora Medical Center in Summit Summit Wisconsin United States 53066
    249 UW Cancer Center at ProHealth Care Waukesha Wisconsin United States 53188
    250 Aspirus Regional Cancer Center Wausau Wisconsin United States 54401
    251 Aurora West Allis Medical Center West Allis Wisconsin United States 53227
    252 Froedtert West Bend Hospital/Kraemer Cancer Center West Bend Wisconsin United States 53095
    253 London Regional Cancer Program London Ontario Canada N6A 4L6
    254 University Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
    255 The Research Institute of the McGill University Health Centre (MUHC) Montreal Quebec Canada H3H 2R9
    256 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • Canadian Cancer Trials Group
    • NRG Oncology

    Investigators

    • Principal Investigator: Loren K Mell, NRG Oncology

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT03258554
    Other Study ID Numbers:
    • NCI-2017-01522
    • NCI-2017-01522
    • NRG-HN004
    • NRG-HN004
    • U10CA180868
    First Posted:
    Aug 23, 2017
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Apr 1, 2022

    Study Results

    No Results Posted as of Aug 23, 2022