Study of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Study Overview
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Brief Summary
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This study is conducted in Japanese newly diagnosed locally advanced SCCHN patients in order to assess tolerability and feasibility of Cetuximab plus concomitant boost radiotherapy (RT) regimen (the study treatment) and its safety profile (i.e. AEs: adverse events). In addition, efficacy (i.e. anti-tumor effect) of the study treatment is also evaluated.

Official Title
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Open-label, Non-randomized, Non-controlled, Multicenter Phase II Study Investigating Cetuximab in Combination With Concomitant-boost Radiotherapy as First-line Treatment for Japanese Patients With Newly Diagnosed Locally Advanced SCCHN.

Conditions
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Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, or larynx. The patient has been confirmed Epidermal Growth Factor Receptor expressing in tumor specimen by immunohistochemistry. The patient has stage III or IV disease (Unio Internationalis Contra Cancrum / International Union against Cancer Tumor-Lymph Nodes-Metastases classification) with an expected survival of ≥ 12 months. The patient has at least bi-dimensionally measurable disease. The patient is medically suitable to withstand a course of the definitive radiation therapy. The patient aged ≥ 20 years old at informed consent The patient's Karnofsky performance status is ≥ 60 Hemoglobin ≥ 9g/dL Neutrophil ≥ 1500/mm^3 Platelet ≥ 100,000/mm^3 Total Bilirubin ≤ 1.5 mg/dL Aspartate Aminotransferase ≤ 2 x the upper limit of normal Alanine Aminotransferase ≤ 2 x the upper limit of normal Serum creatinine ≤ 1.5 mg/dL Serum calcium concentration: within normality The patient is eligible if disease free from a previously treated malignancy for greater than three years. The patient agrees to use effective contraception if procreative potential exists. The patient has given signed informed consent The patient who is a Japanese with Japanese citizenship Exclusion Criteria: The patient has evidence of distant metastatic disease. The patient who has any metastatic disease documented by Magnetic Resonance Imaging for the head and neck, and Computed Tomography for the chest and abdomen should be excluded. The patient has squamous cell carcinoma arising in the nasopharynx or oral cavity. The patient has received prior systemic chemotherapy within the last three years. The patient has undergone previous surgery for the tumor under study other than biopsy. The patient has received prior radiation therapy to the head and neck. The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection. The patient is pregnant or breast feeding. The patient has received prior Cetuximab or murine monoclonal antibody (including chimeric antibody) therapy or a history of severe hypersensitivity to any component of Cetuximab solution for Injection. The patient has a medical or psychological condition that would not permit the patient to complete the study or sign informed consent (including drug abuse). The patient has uncontrolled diabetes mellitus, malignant hypertension, or liver failure. The patient has or has suffered from a pulmonary fibrosis, acute pulmonary disorder, or interstitial pneumonia. The patient has an active infection (infection requiring intravenous anti-bacterial, anti-fungus, or anti-viral agent), or known and declared Human Immunodeficiency Virus infection. The patient has a clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency The patient has a dental disease which requires incision and drainage. The patient has active multiple cancers (excluding skin cancer except for melanoma, and carcinoma in situ of the cervix or the digestive tract) in the last 3 years. The patient has been received some investigational medication within 30 days before study entry.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab With Radiotherapy<br> | Drug: Cetuximab<br>* Patients receive Cetuximab at an initial dose of 400 mg/m^2 of Cetuximab to be infused 6 or 7 days before starting radiotherapy, followed by subsequent weekly infusions at a dose of 250 mg/m^2 of Cetuximab and RT (72.0 Gy total in 42 fractions) for the next 6 weeks of the treatment course. Subjects will receive Cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn. If RT is delayed, administration of Cetuximab every 7 days is continued. If RT is discontinued for any reason, treatment with Cetuximab monotherapy every 7 days is continued.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion Rate | Number of subjects who complete ≥70% of Cetuximab planned dose administration in terms of relative dose intensity of Cetuximab and full dose of RT ≤2 weeks over planned schedule in terms of RT duration ≤8 weeks, divided by the the number of subjects in the ITT/Safety population | time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response Rate | Number of subjects experiencing a Complete Response (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (>=50% decrease of the sum of the product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions) at 8 weeks post radiotherapy (confirmed by repeat assessment at week 12) based on imaging according to modified World Health Organisation criteria as assessed independently by the Efficacy and Safety Evaluation Committee, divided by the number of subjects in the ITT/safety population | best response was determined at week 8 post radiotherapy, for subjects with complete or partial response a confirmation in week 12 post radiotherapy was required | 
| Safety - Number of Patients Experiencing Any Adverse Event | Please refer to Adverse Events section for further details | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 
| Safety - Number of Patients Experiencing Any Grade 4 Adverse Event | Severity was assessed according to the toxicity criteria defined in the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE), Version 3.0, where grade 1 denoted mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. In the case of adverse events not contained within the NCI-CTCAE, the investigator was responsible for assessing the severity of the AE (grades 1 to 4) based on the jeopardy to the subject's health and well-being, and the ability of the subject to function during the event. | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 
| Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction | Skin reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 
| Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction | Infusion related reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN)