Study of Cetuximab in Combination With Chemotherapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Study Overview
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Brief Summary
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The primary objective of this trial is to assess the antitumor activity of cetuximab when given in combination with cisplatin + 5-Fluorouracil (5-FU) for the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) in Japanese subjects.

Official Title
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Open-label, Single-arm, Multicenter, Phase II Study Investigating Cetuximab in Combination With Chemotherapy in the First-line Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) in Japanese Subjects

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Cisplatin/Carboplatin
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of SCCHN Confirmed epidermal growth factor receptor (EGFR) expression in tumor tissue by immunohistochemistry (IHC) Expected survival is more than 6 months Presence of at least 1 bidimensionally measurable lesion either by computed tomography (CT) scan or magnetic resonance imaging (MRI) Recurrent and/or metastatic SCCHN not suitable for local therapy Greater than or equal to (>=) 20 years of age Karnofsky performance status (KPS) >= 70% at trial entry Neutrophils: >= 1500 per millimeter^3 (1,500/mm^3); platelet count >= 100,000/mm^3; and hemoglobin >= 9 gram per deciliter (g/dL) Total bilirubin less than or equal to (<=) 2 * upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 * ULN Creatinine clearance >60 milliliter per minute (mL/min).Calculated based on formulae such as the Cockroft-Gault formula for creatinine clearance Serum calcium within normal range (If serum albumin < 4.0 g/dL, the following adjusted serum calcium concentration should be within normality: Adjusted serum calcium concentration = actual serum calcium (milligram per deciliter [mg/dL]) - 0.8 * [actual serum albumin (g/dL) - 4] Effective contraception if risk of conception exists (applicable for both male and female subjects) Signed written informed consent Japanese (with Japanese citizenship) Exclusion Criteria: Nasopharyngeal carcinoma Prior systemic chemotherapy, except if given as part of a multimodal treatment, which was completed more than 6 months prior to trial entry Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry Pregnancy (absence to be confirmed by serum/urine human chorionic gonadotropin [HCG] test) or breastfeeding Known hypersensitivity or allergic reaction against any of the components of the trial treatment including excipients Uncontrolled diabetes, malignant hypertension (defined as systolic blood pressure >= 180 millimeter of mercury [mmHg] and/or diastolic blood pressure >= 130 mmHg under resting conditions) or liver failure Pulmonary fibrosis, acute lung injury or interstitial pneumonia, or with previous medical history of these states Active infection, (infection requiring IV antibiotics, antibacterial, antifungal, or antiviral agent), including active tuberculosis, or known and declared human immunodeficiency virus (HIV) 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 Current other squamous cell carcinoma (SCC) or previous other malignancy (excluding skin cancer except for melanoma and carcinoma in situ of the cervix or digestive tract) within the last 5 years Intake of any investigational medication within 30 days before trial entry Other concomitant anticancer therapies Documented or symptomatic brain or leptomeningeal metastasis Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent including known drug abuse Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or EGFR targeting therapy Legal incapacity or limited legal capacity Other protocol-defined exclusion criteria may apply

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 + Cisplatin/Carboplatin + Fluorouracil (5-FU)<br> | Drug: Cetuximab<br>* The initial dose of cetuximab will be 400 milligram per square meter (mg/m^2) as an intravenous (IV) infusion over 120 minutes. Subsequent weekly doses will be 250 mg/m^2 as an IV infusion over 60 minutes.<br>Drug: Cisplatin/Carboplatin<br>* Subjects will receive 100 mg/m^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle. If subject developed non-hematological toxicities to cisplatin, carboplatin (area under curve 5 [AUC5]) will be administered as an IV infusion over 60 to 120 minutes on Day 1 of each 3-week treatment cycle.<br>Drug: 5-Fluorouracil<br>* Subjects will receive 1000 mg/m^2 per day 5-FU as a continuous IV infusion over 24 hours from day 1 to day 4 of each 3-week treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria | Percentage of participants experiencing a complete response [CR] (complete disappearance of measurable and evaluable disease without new lesions) or partial response [PR] (greater than or equal to 50 percent decrease in the sum of the products of diameters [SOPD] of index lesions compared to the baseline SOPD, with no evidence of PD) confirmed by a subsequent assessment no less than 28 days after criteria for response were first met based on modified WHO criteria as assessed by Independent Review Committee (IRC). | Evaluations performed every 6 weeks until progressive disease (PD) reported between day of first participant treated, until cut-off date, 02 March 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST as assessed by IRC. CR are those that persist on repeat imaging study at least 28 days after initial documentation of response. PR are those with greater than or equal to 30 percent decrease in the SOPD of index lesions compared to the baseline SOPD, with no evidence of PD. | Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011 | 
| Disease Control Rate | Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (>=50 percent decrease in sum of the products of diameters [SOPD] of index lesions compared to baseline SOPD, with no evidence of PD) confirmed by subsequent assessment no less than 28 days after criteria for response were first met) or stable disease [SD] (neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD) at least once no less than 42 days after first dose of trial treatment based on modified WHO criteria as assessed by IRC. | Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011 | 
| Duration of Response | Duration of response according to modified WHO criteria as assessed by IRC was defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death when death occurred within 60 days of the last tumor assessment or first administration of trial treatment (whichever was last). | Time from first assessment of CR or PR to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011 | 
| Progression-Free Survival (PFS) Time | The PFS time according to modified WHO criteria as assessed by IRC was defined as duration from first administration of trial treatment until PD (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment. | Time from first administration of trial treatment to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011 | 
| Overall Survival (OS) Time | Time from first administration of trial treatment to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier. | Time from first administration of trial treatment or last day known to be alive, reported between day of first participant treated, until cut-off date, 02 March 2011 | 
| Time to Treatment Failure | Time to treatment failure according to modified WHO criteria as assessed by IRC was defined as the time from first administration of trial treatment until the date of the first occurrence of one of the events defining treatment failure: PD assessed by the investigator, discontinuation of treatment due to PD, discontinuation of treatment due to an adverse event (AE), start of any new anticancer therapy, or withdrawal of consent or death within 60 days of the last tumor assessment or first administration of trial treatment. | Time from first administration of trial treatment to treatment failure or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent and/or metastatic, SCCHN