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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genmab
ClinicalTrials.gov Identifier:
NCT01054625
First received: January 15, 2010
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: zalutumumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genmab:

Primary Outcome Measures:
  • Maximum Plasma Concentration of Zalutumumab After Fourth Infusion [ Time Frame: Pre and post infusion after weekly administration of zalutumumab during 28 days ] [ Designated as safety issue: Yes ]
    PK samples are taken: pre and post infusion on days 0, 14, 21 and 28 plus at +3 and +12 hours on days 0 and 28. A single PK sample is taken on days between these treatments and 8 more are taken over 3 weeks after treatment on day 28.


Secondary Outcome Measures:
  • Area Under Curve 0-7 Days [ Time Frame: 0-7 days ] [ Designated as safety issue: No ]
  • Area Under Curve 0-21 Days [ Time Frame: 0-21 days ] [ Designated as safety issue: No ]
  • Elimination Half-life [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Clearance [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Apparent Volume of Distribution During the Terminal Phase [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Apparent Volume of Distribution at Steady State [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: March 2010
Study Completion Date: October 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: zalutumumab 4 mg/kg
zalutumumab 4 mg/kg iv single infusion week 1,3, 4 and 5
Biological: zalutumumab
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.
Experimental: zalutumumab 8 mg/kg
zalutumumab 8 mg/kg iv single infusion week 1, 3, 4 and 5
Biological: zalutumumab
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.
Experimental: zalutumumab 16 mg/kg
zalutumumab 16 mg/kg iv single infusion week 1, 3, 4 and 5
Biological: zalutumumab
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01054625

Locations
Belgium
Cliniques Universitaires SaintLuc
Brussels, Belgium, 1200
Uz Leuven - Campus Gasthuisberg
Leuven, Belgium, 3000
Hungary
Uzsoki Hospital
Budapest, Hungary, H-1145
Vas Megye es Szombathely
Szombathely, Hungary, 9700
Slovakia
Narodny onkologicky ustav
Bratislava, Slovakia, 833 10
FN Tnava
Trnava, Slovakia, 917 75
United Kingdom
St James's Institute of Oncology
Leeds, United Kingdom, LS9 7TF
Sponsors and Collaborators
Genmab
Investigators
Principal Investigator: Jean-Pascal Machiels, MD, PhD Cliniques Universitaires SaintLuc, Belgium
  More Information

No publications provided

Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT01054625     History of Changes
Other Study ID Numbers: GEN211
Study First Received: January 15, 2010
Results First Received: August 8, 2013
Last Updated: November 13, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy
Slovakia: State Institute for Drug Control

Keywords provided by Genmab:
Squamous Cell Carcinoma of the Head and Neck
Head and Neck Cancer
Head and Neck Neoplasms
anti-EGFr monoclonal antibody
Zalutumumab

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014