Zalutumumab Pharmacokinetics (PK) in Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Study Overview
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Brief Summary
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This study is to support current and future Zalutumumab studies by increasing the Pharmacokinetic (PK) knowledge of the drug. PK is the study of how a drug is absorbed (taken up), distributed (moved around), metabolised (broken down) and excreted (removed) by the body, in relation to time. The first PK trial only went up to 8 mg/kg, and, as there has been some indication that the PK profile for the higher and lower doses is different, this needs to be further evaluated. Furthermore, there is a need for more PK data on dosing with 16mg/kg. The aim with this study is therefore to evaluate the PK profiles at different doses of Zalutumumab and the amount of drug in the blood at different time points after single and multiple doses. The results of this study, combined with data from completed and ongoing Zalutumumab studies, will enable us to provide patients with an effective treatment option which may significantly prolong their survival and/or improve their quality of life.

Detailed Description
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This study is to look at the Pharmacokinetics (PK) of Zalutumumab in patients with Head and Neck Cancer. 26 participants will be treated with the study drug Zalutumumab at 4 different doses. Zalutumumab will be given at day 0, day 14, day 21 and day 28. Blood samples (for PK and to check the participant's safety) will be taken before drug is given. Blood samples for PK only will be taken directly after drug is given at all treatment visits and also at +3hr and +12hrs on day 0 and day 28 which may require an overnight stay. Blood samples for PK only are also taken on days between treatments. After treatment on day 28, eight more blood samples will be taken over 3 weeks. On day 49 participants may enter an optional extended treatment period receiving the drug weekly until it is no longer appropriate for the participant (doctor/participant decision or cancer has advanced). Dosing in the extended treatment period will start at 16mg/kg. The correct dose for the participant will be checked at each visit by looking for the presence and severity of skin rash. This is a common side effect of medicines like Zalutumumab which block the Epidermal Growth Factor Receptor. The severity of the skin rash is used as a guide for dosing. A mild rash could mean more medication is needed, a severe rash will mean the participant needs a break from the medication. End of study is 8 weeks after the last dose of Zalutumumab and blood samples will be taken +4weeks and +8weeks after the last dose of drug.

Official Title
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An Open-label, Multi-Center, Phase I/II Trial Investigating the Pharmacokinetic Profile of Zalutumumab, a Human Monoclonal Epidermal Growth Factor Receptor Antibody in Non-curable Patients With SCCHN

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: zalutumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years. Diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, considered incurable with standard therapy. Diagnosis will have been confirmed using a biopsy of the tumour. Patients having, based on the investigators judgment, had disease progression and for whom curative therapy is not possible. Patients with a WHO performance status ≤ 2 and a life expectancy of greater than 3 months. Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out. Exclusion Criteria: Patients previously treated with any Epidermal Growth Factor Receptor (EGFR) targeted therapy such as anti-EGFR monoclonal antibodies or small molecule inhibitors within 6 months prior to visit 2 (first treatment). Received the following treatments within 4 weeks prior to Visit 2 (first treatment): Cytotoxic or cytostatic anticancer chemotherapy Total tumor resection Radiotherapy of > 50 Gy to gross tumor volume Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, sinusitis, and tuberculosis Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1 (screening), congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease History of significant cerebrovascular disease Known HIV infection Known hepatitis B and/or hepatitis C Screening laboratory values: Neutrophils < 1.5 x109/l Platelets < 75 x109/l ALAT > 2.5 times the upper limit of normal (unless known liver metastases exceptions will be dealt with on a case by case basis) ALP > 2.5 times the upper limit of normal (unless known liver metastases exceptions will be dealt with on a case by case basis) Bilirubin > 1.5 times the upper limit of normal Creatinine clearance < 50 ml/min (measured or calculated by the CockgroftGault method) Patients who have received treatment with any non-marketed drug substance within 4 weeks before Visit 1(screening) Current participation in any other interventional clinical study Patients with a BMI ≥ 30 kg/m2 Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) Breast feeding women or women with a positive pregnancy test at Visit 1 (screening) Women of childbearing potential not willing to use adequate contraception such as hormonal birth control or intrauterine device during study.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: zalutumumab 4 mg/kg<br>zalutumumab 4 mg/kg iv single infusion week 1,3, 4 and 5 | Biological: zalutumumab<br>* Zalutumumab is a clear to opalescent liquid. It is intended for intravenous infusion following dilution in sterile, pyrogen free, 0.9% NaCl. Patients will be treated at a specified dose of Zalutumumab over a period of 7 weeks. The dose will be 4mg/kg, 8mg/kg or 16mg/kg depending on when they enter the study. The study will begin with 6 patients on 4mg/kg, then 10 patients on 8mg/kg and lastly 10 patients on 16mg/kg.<br>|
| Experimental: zalutumumab 8 mg/kg<br>zalutumumab 8 mg/kg iv single infusion week 1, 3, 4 and 5 | Biological: zalutumumab<br>* Zalutumumab is a clear to opalescent liquid. It is intended for intravenous infusion following dilution in sterile, pyrogen free, 0.9% NaCl. Patients will be treated at a specified dose of Zalutumumab over a period of 7 weeks. The dose will be 4mg/kg, 8mg/kg or 16mg/kg depending on when they enter the study. The study will begin with 6 patients on 4mg/kg, then 10 patients on 8mg/kg and lastly 10 patients on 16mg/kg.<br>|
| Experimental: zalutumumab 16 mg/kg<br>zalutumumab 16 mg/kg iv single infusion week 1, 3, 4 and 5 | Biological: zalutumumab<br>* Zalutumumab is a clear to opalescent liquid. It is intended for intravenous infusion following dilution in sterile, pyrogen free, 0.9% NaCl. Patients will be treated at a specified dose of Zalutumumab over a period of 7 weeks. The dose will be 4mg/kg, 8mg/kg or 16mg/kg depending on when they enter the study. The study will begin with 6 patients on 4mg/kg, then 10 patients on 8mg/kg and lastly 10 patients on 16mg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration of Zalutumumab After Fourth Infusion |  | Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days) | 
| Area Under the Curve 0-7 Days |  | Pre-dose and post dose at multiple timepoints from start of first infusion up to end of last infusion (Day 0 to 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve 0-21 Days |  | Pre-dose and post dose at multiple timepoints from start of fourth infusion up to end of last infusion (Day 0 to 21) | 
| Elimination Half-life |  | Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days) | 
| Clearance |  | Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days) | 
| Apparent Volume of Distribution During the Terminal Phase |  | Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days) | 
| Apparent Volume of Distribution at Steady State |  | Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Carcinoma of the Head and Neck, Head and Neck Cancer, Head and Neck Neoplasms, anti-EGFr monoclonal antibody, Zalutumumab