RESEARCH STUDIES & Clinical Trials

Clinical Trial ID: NCT03258554 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

Status

Open

Description

This randomized phase II/III trial studies 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

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. 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. 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.

Treatment

Active Comparator: Cetuximab + Radiation Therapy Patients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 courses 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. Experimental: Durvalumab + Radiation Therapy Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

Conditions

Other

Phases

II/III

Therapies

Drugs

Age Group

Adult

Main Investiagtor

Neki, Anterpreet

Practice

Head/Neck

Scope

National

Participating Institutions

Baptist MD Anderson Cancer Center

Eligibility

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 within 60 days prior to step 1 registration - Patients must have stage III-IVB head and neck squamous cell carcinoma (HNSCC) (American Joint Committee on Cancer [AJCC] seventh [7th] edition) - 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 - Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 - Platelets >= 100,000 cells/mm^3 - Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times institutional upper limit of normal - Serum bilirubin =< 1.5 x institutional upper limit of normal - 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 - For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration - The patient or a legally authorized representative must provide study-specific informed consent 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 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 - 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 - Potassium < 3.5 mmol/L or > 6 mmol/L - Fasting glucose < 40 mg/dl or > 400 mg/dl - Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl - Magnesium < 0.9 mg/dl or > 3 mg/dl - 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 - 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 - History of allogenic organ transplantation - Uncontrolled hypertension - Uncontrolled cardiac arrhythmia - Uncontrolled serious chronic gastrointestinal condition associated with diarrhea - Other eligibility criteria may apply per study protocol

Nct ID Number

NCT03258554

Secondary Trial ID Number

Keywords

Treatment

More Information

clinicaltrials.gov

“The support team gave not only me but my family a sense of peace.”

—David Smith, Patient

At Baptist MD Anderson, you can rely on our cancer experts to deliver the complex, coordinated care needed to address your condition. Learn more about Patricia’s story as well as others from our patients.