An Open-label, International, Multi-Center, Phase I/II, Dose-escalation Trial Investigating the Safety of Zalutumumab, a Human Monoclonal Epidermal Growth Factor Receptor Antibody in Combination with Radiotherapy, in Patients with Stage III, IVa or IVb Locally Advanced Squamous Cell Carcinoma of the Head and Neck Ineligible for Platinum based Chemotherapy - Zalutumumab in combination with radiotherapy in SCCHN patients ineligible for platinum based chemoth

Conditions: Stage III, IVa or IVb Locally Advanced Squamous Cell Carcinoma of the Head and Neck Ineligible for Platinum based Chemotherapy
MedDRA version: 9.1Level: LLTClassification code 10023860Term: Laryngeal squamous cell carcinoma stage III
MedDRA version: 9.1Level: LLTClassification code 10023861Term: Laryngeal squamous cell carcinoma stage IV

Registration Number: EUCTR2008-000781-23-BE

Lead Sponsor: Genmab A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 30

Inclusion Criteria

1) Patients with histologically or cytologically confirmed diagnosis of locally advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx stage III, IVa or IVb
2) Measurable disease defined as one or more target lesions according to RECIST based on CT scan or MRI and clinical evaluation
3) Eligible for intended curative radiotherapy
4) Patients considered ineligible for platinum based chemotherapy based on investigator’s judgment
5) Age > 18 years
6) 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Prior radiotherapy to the head and neck area
2) Prior chemotherapy administered for cancer in the head and neck area
3) Prior targeted therapy (e.g. EGFr antibodies or EGFr inhibitors)
4) Received the following treatments within 4 weeks prior to Visit 2:
a. Retinoic acid
b. Other immunosuppressive drugs (e.g. drugs interfering with the functions of T cells, IL-2 or equivalent)
c. Any non-marketed drug substance
5) Past or current malignancy other than SCCHN, except for:
• Cervical carcinoma Stage 1B or less
• Non-invasive basal cell skin carcinoma
• Squamous cell skin carcinoma
• Stage 1 or 2 treated prostate cancer with PSA in the normal range for >2 years post treatment
• Malignant melanoma with a complete response duration of > 10 years
• Other cancer diagnoses with a complete response duration of > 5 years
6) Metastatic SCCHN disease
7) Chronic or current infectious disease such as, but not limited to, chronic renal infection, and tuberculosis
8) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months before Visit 1, congestive heart failure, and arrhythmia requiring anti-arrhythmic therapy, with the exception of extra systoles or minor conduction abnormalities
9) Significant concurrent, uncontrolled medical condition including, but not limited to, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease considered to preclude trial treatment and/or compliance according to the Investigator’s opinion, or any other condition preventing therapy according to the Investigator’s opinion
10) Known HIV positive
11) Known active hepatitis B and/or hepatitis C
12) Screening laboratory values:
• Neutrophils < 1.5 x 109/L
• Platelets < 100 x109/L
• Hemoglobin < 6 mmol/L
13) Current participation in any other interventional clinical study
14) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency, or psychological disorder)
15) Known or suspected hypersensitivity to components of the investigational medicinal product
16) Breast feeding women or women with a positive pregnancy test at screening blood sample
17) Males not willing to use adequate contraception during study and for 12 months after last dose of zalutumumab or women of childbearing potential not willing to use adequate contraception as hormonal birth control or intrauterine device during study and for 12 months after last dose of zalutumumab

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of repeat dosing and establish the maximum tolerated dose (MTD) of zalutumumab in combination with radiotherapy in patients with stage III, IVa or IVb locally advanced squamous cell carcinoma of the head and neck ineligible for platinum based chemotherapy;Secondary Objective: To evaluate the pharmacokinetic (PK) profile and the efficacy of repeat dosing of zalutumumab in combination with radiotherapy in patients with stage III, IVa or IVb locally advanced squamous cell carcinoma of the head and neck ineligible for platinum based chemotherapy;Primary end point(s): 1) Adverse events (AEs) including skin rash (CTCAE grading, onset, and duration), acute and late radiation toxicities<br>2) Host immune response: Human Anti Human Antibodies (HAHA)<br>

Secondary Outcome Measures

Name	Time	Method

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