- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01054625
Zalutumumab Pharmacokinetics (PK) in Squamous Cell Carcinoma of the Head and Neck (SCCHN)
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
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.
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Brussels, Belgium, 1200
- Cliniques Universitaires SaintLuc
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Leuven, Belgium, 3000
- UZ Leuven - Campus Gasthuisberg
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Budapest, Hungary, H-1145
- Uzsoki Hospital
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Szombathely, Hungary, 9700
- Vas Megye es Szombathely
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Bratislava, Slovakia, 833 10
- Narodny Onkologicky Ustav
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Trnava, Slovakia, 917 75
- FN Tnava
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Leeds, United Kingdom, LS9 7TF
- St James's Institute of Oncology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: zalutumumab 4 mg/kg
zalutumumab 4 mg/kg iv single infusion week 1,3, 4 and 5
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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.
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Experimental: zalutumumab 8 mg/kg
zalutumumab 8 mg/kg iv single infusion week 1, 3, 4 and 5
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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.
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Experimental: zalutumumab 16 mg/kg
zalutumumab 16 mg/kg iv single infusion week 1, 3, 4 and 5
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Maximum Plasma Concentration of Zalutumumab After Fourth Infusion
Time Frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Area Under the Curve 0-7 Days
Time Frame: Pre-dose and post dose at multiple timepoints from start of first infusion up to end of last infusion (Day 0 to 7)
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Pre-dose and post dose at multiple timepoints from start of first infusion up to end of last infusion (Day 0 to 7)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Area Under the Curve 0-21 Days
Time Frame: Pre-dose and post dose at multiple timepoints from start of fourth infusion up to end of last infusion (Day 0 to 21)
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Pre-dose and post dose at multiple timepoints from start of fourth infusion up to end of last infusion (Day 0 to 21)
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Elimination Half-life
Time Frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Clearance
Time Frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Apparent Volume of Distribution During the Terminal Phase
Time Frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Apparent Volume of Distribution at Steady State
Time Frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jean-Pascal Machiels, MD, PhD, Cliniques Universitaires SaintLuc, Belgium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GEN211
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Head and Neck Cancer
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Robert FerrisAmgenCompletedHead and Neck Cancer | Cancer of Head and Neck | Head Cancer | Neck Cancer | Neoplasms, Head and Neck | Cancer of the Head and Neck | Cancer of Neck | Upper Aerodigestive Tract Neoplasms | Neck Neoplasms | Cancer of the Head | Cancer of the Neck | UADT Neoplasms | Cancer of Head | Head Neoplasms | Head, Neck Neoplasms | Neoplasms, Head and other conditionsUnited States
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Assiut UniversityRecruitingHead and Neck Cancer | Head and Neck Neoplasms | Cancer of Head and Neck | Neoplasms, Head and Neck | Cancer of the Head and NeckEgypt
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IRCCS Policlinico S. MatteoNestlé Health Science Spain; Akern SrlCompletedHead-neck CancerItaly
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University of California, San FranciscoCompleted
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Chinook Therapeutics, Inc. (formerly Aduro)TerminatedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedHead And Neck CancerUnited States
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National Cancer Institute (NCI)TerminatedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerUnited States
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Centre Oscar LambretUnknownEpidermoid Head and Neck CancerFrance
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Radboud University Medical CenterUnknown
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