Facebook

Twitter

Linkedin

Pinterest

Email

Clinical Trials Search

Back to Search Results

Clinical Trial 19473

Cancer Type: Head & Neck
Study Type: Treatment
NCT#: NCT03258554

Phase: Phase II/III
Principal Investigator: Kish, Julie

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

Randomized Phase II/III Trial of Radiotherapy with Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy with Concurrent Cetuximab in Patients with Stage III-IVB Head and Neck Cancer with a Contraindication to Cisplatin

Summary

The purpose of this study is to see how well radiation therapy works with durvalumab or cetuximab in treating patients with stage III-IVB head and neck cancer who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as durvalumab and cetuximab, 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.

Objective

Primary Objectives: 1.1.1 Lead-In: 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. 1.1.2 Phase II: To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves PFS compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. 1.1.3 Phase 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. 1.2 Secondary Objectives: 1.2.1 To compare toxicity using CTCAE and PRO-CTCAE between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab. 1.2.2 To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1. 1.2.3 To compare overall survival, response (at 4-month FDG-PET-CT), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and ù score. 1.2.4 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. 1.2.5 To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT) will have less decline in swallowing related QOL using the 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. 1.2.6 To compare swallowing related performance and function short and long term using the PSS-HN. 1.2.7 To evaluate gastrostomy tube retention rates between arms. 1.3 Exploratory Objectives: 1.3.1 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. 1.3.2 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. 1.3.3 To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24 months from end of RT) using the EORTC HN35 swallowing domain and MDADI (subscales) between arms in patients with locoregionally advanced HNC who have a contraindication to cisplatin. 1.3.4 To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and PRO-CTCAE. 1.3.5 To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE. 1.3.6 To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the EQ5D-5L.

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy; Radiotherapy

Medications

AMP-514 (Durvalumab); Cetuximab (); Durvalumab (); Erbitux (Cetuximab); MEDI4736 (Durvalumab)

Inclusion Criteria

Participants must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary within 60 days prior to step 1 registration.

Must have stage III-IVB head and neck squamous cell carcinoma (HNSCC) (American Joint Committee on Cancer [AJCC] seventh [7th] edition) within 60 days prior to step 1 registration.

Age >= 18 with an absolute or relative contraindication to cisplatin within 30 days prior to Step 1 registration.

Adequate laboratory values.

For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration.

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 prior to step 2 registration. 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.

Additional criteria may apply.

Exclusion Criteria

Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer).

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

Prior immunotherapy.

Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer.

Distant metastases.

If both of the following conditions are present, the patient is ineligible: > Zubrod performance status >= 3.

Patients with oral cavity cancer if the patient is medically operable and resection of the primary tumor is considered technically feasible.

Does not meet adequate laboratory values within 14 days of 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.

Clinically apparent jaundice and/or known coagulation defects.

Active or prior documented autoimmune or inflammatory. Some exceptions may apply.

History of active primary immunodeficiency.

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); women who are breastfeeding.

Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or any of study drug excipients.

History of (non-infectious) pneumonitis that required steroids or current pneumonitis, or allogenic organ transplantation.

Uncontrolled hypertension, or cardiac arrhythmia, or serious chronic gastrointestinal condition associated with diarrhea.

Active infection including tuberculosis; hepatitis B; 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)