CompletedNCT01054625Updated Aug 3, 2023Results posted

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

A Phase 1/2 interventional study of zalutumumab in Head and Neck Cancer, sponsored by Genmab. Completed at 7 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-03.

Sponsored by Genmab · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 31
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the 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.

Conditions studied

Head and Neck Cancer

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Keywords

Squamous Cell Carcinoma of the Head and Neck
Head and Neck Cancer
Head and Neck Neoplasms
anti-EGFr monoclonal antibody
Zalutumumab

In context

Head and Neck Neoplasms

2,344 studies on the registry are indexed under Head and Neck Neoplasms; 551 are open to participants now.

This study's enrollment of 31 is below the median of 47 across 1,751 interventional studies indexed under Head and Neck Neoplasms.

Browse Head and Neck Neoplasms studies →

Lead sponsor

Genmab is the lead sponsor of 67 studies on the registry; 14 are open to participants now.

Of its 23 completed or terminated interventional studies of FDA-regulated products, 12 (52%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 31 participants (actual)

Study arms

Experimental
zalutumumab 4 mg/kg
zalutumumab 4 mg/kg iv single infusion week 1,3, 4 and 5
Biological: zalutumumab
Experimental
zalutumumab 8 mg/kg
zalutumumab 8 mg/kg iv single infusion week 1, 3, 4 and 5
Biological: zalutumumab
Experimental
zalutumumab 16 mg/kg
zalutumumab 16 mg/kg iv single infusion week 1, 3, 4 and 5
Biological: zalutumumab

Interventions

Biologicalzalutumumab
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.

What researchers measure

Primary outcomes

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)
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)

Secondary outcomes

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)
Elimination Half-life
Time frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
Clearance
Time frame: 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
Time frame: 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
Time frame: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)

Results

Posted Jan 3, 2014

Participant flow

Participant flow — Overall Study
Milestone	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Started	8	12	10
Completed	6	9	9
Not completed	2	3	1

Outcome measures

PrimaryMaximum 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)
Reported as:: Geometric mean · mg/L

Maximum Plasma Concentration of Zalutumumab After Fourth Infusion
mg/L	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Maximum Plasma Concentration of Zalutumumab After Fourth Infusion	104.3 ± 31	258.1 ± 28	494.3 ± 50

PrimaryArea 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)
Reported as:: Geometric mean · h*mg/L

Area Under the Curve 0-7 Days
h*mg/L	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Area Under the Curve 0-7 Days	9308 ± 47	25091 ± 36	52158 ± 57

SecondaryArea 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)
Reported as:: Geometric mean · h*mg/L

Area Under the Curve 0-21 Days
h*mg/L	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Area Under the Curve 0-21 Days	12728 ± 60.9	44275 ± 43.1	105960 ± 58.8

SecondaryElimination Half-life

Time frame:: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
Reported as:: Geometric mean · h

Elimination Half-life
h	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Elimination Half-life	63 ± 71.7	193 ± 37.7	283 ± 38.0

SecondaryClearance

Time frame:: Pre-dose and post dose at multiple timepoints up to end of the study (up to 30 days)
Reported as:: Geometric mean · L/h

Clearance
L/h	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Clearance	0.025 ± 56.3	0.018 ± 25.7	0.019 ± 40.6

SecondaryApparent 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)
Reported as:: Geometric mean · L

Apparent Volume of Distribution During the Terminal Phase
L	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Apparent Volume of Distribution During the Terminal Phase	2.28 ± 49	4.99 ± 35	7.83 ± 56

SecondaryApparent 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)
Reported as:: Geometric mean · L

Apparent Volume of Distribution at Steady State
L	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Apparent Volume of Distribution at Steady State	3.23 ± 27	4.86 ± 29	7.72 ± 60

Adverse events

Collected over From first dose until the end of the safety follow-up period (30 days after last dose) up to 60 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Zalutumumab 4 mg/kg	—	7/8 (87.5%)	8/8 (100%)
Zalutumumab 8 mg/kg	—	5/12 (41.7%)	12/12 (100%)
Zalutumumab 16 mg/kg	—	3/10 (30%)	10/10 (100%)

Most frequent serious events

Showing 10 of 14

Most frequent serious events
Event	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
Disease progressionGeneral disorders	3/8	4/12	3/10
Infusion related reactionGeneral disorders	2/8	0/12	1/10
PyrexiaGeneral disorders	1/8	0/12	0/10
PneumoniaInfections and infestations	1/8	0/12	0/10
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders	1/8	0/12	0/10
Upper respiratory tract infectionInfections and infestations	0/8	0/12	1/10
Foot fractureInjury, poisoning and procedural complications	0/8	0/12	1/10
ArthralgiaMusculoskeletal and connective tissue disorders	0/8	0/12	1/10
Confusional statePsychiatric disorders	0/8	0/12	1/10
Lung infectionInfections and infestations	0/8	1/12	0/10

Most frequent other events

Showing 10 of 35

Most frequent other events
Event	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg
RashSkin and subcutaneous tissue disorders	1/8	6/12	6/10
FatigueGeneral disorders	2/8	5/12	2/10
DysphagiaGastrointestinal disorders	3/8	1/12	1/10
Weight decreasedInvestigations	3/8	1/12	0/10
Decreased appetiteMetabolism and nutrition disorders	3/8	4/12	2/10
HeadacheNervous system disorders	0/8	4/12	2/10
Dermatitis acneiformSkin and subcutaneous tissue disorders	0/8	4/12	2/10
AnaemiaBlood and lymphatic system disorders	0/8	2/12	3/10
ConstipationGastrointestinal disorders	2/8	1/12	2/10
DiarrhoeaGastrointestinal disorders	2/8	3/12	2/10

Baseline characteristics

Thirty of the 31 enrolled participants were included in the full analysis set (FAS) population. One participant was excluded from the FAS because he died before the first infusion of trial drug.

Age, Categorical
Age, Categorical(Participants)	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg	Total
<=18 years	0	0	0	0
Between 18 and 65 years	6	7	8	21
>=65 years	2	5	2	9

Age, Continuous
Age, Continuous(years)	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg	Total
Mean	57 ± 8	63 ± 11	59 ± 5	60 ± 9

Sex: Female, Male
Sex: Female, Male(Participants)	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg	Total
Female	3	1	0	4
Male	5	11	10	26

Region of Enrollment
Region of Enrollment(participants)	Zalutumumab 4 mg/kg	Zalutumumab 8 mg/kg	Zalutumumab 16 mg/kg	Total
Hungary	1	1	0	2
Slovakia	0	1	3	4
Belgium	6	7	6	19
United Kingdom	1	3	1	5

Study locations

7 sites

Cliniques Universitaires SaintLuc
Brussels, 1200, Belgium
Uz Leuven - Campus Gasthuisberg
Leuven, 3000, Belgium
Uzsoki Hospital
Budapest, H-1145, Hungary
Vas Megye es Szombathely
Szombathely, 9700, Hungary
Narodny onkologicky ustav
Bratislava, 833 10, Slovakia
FN Tnava
Trnava, 917 75, Slovakia
St James's Institute of Oncology
Leeds, LS9 7TF, United Kingdom

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 3, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01054625
Lead sponsor: Genmab
Responsible party: Sponsor
First posted: Jan 22, 2010
Start date: Mar 2010
Primary completion: Jul 2011
Completion: Oct 2011
Results posted: Jan 3, 2014
Last update: Aug 3, 2023

Study contacts

Jean-Pascal Machiels, MD, PhD

principal investigator · Cliniques Universitaires SaintLuc, Belgium

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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