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squamous cell carcinoma
squamous cell carcinoma of the head and neck
head and neck cancer
intensity-modulated radiation therapy
advanced head and neck squamous cell carcinoma
advanced head and neck cancer
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
or cetuximab, may help the body's immune system attack the cancer, and 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.
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)
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
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.
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
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.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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