An Open label single arm trial investigating zalutumumab, a Human Monoclonal Anti-EGF receptor Antibody, in combination with Best Supportive Care, in Patients with Non-Curable Squamous Cell Carcinoma of the Head and Neck who have Failed Standard Platinum-based Chemotherapy. - Zalutumumab in non-curable Patients with SCCHN

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000582-39-DE
• Date of registration: 28/08/2008
• Prospective Registration: Yes
• Primary sponsor: Genmab A/S
• Public title: An Open label single arm trial investigating zalutumumab, a Human Monoclonal Anti-EGF receptor Antibody, in combination with Best Supportive Care, in Patients with Non-Curable Squamous Cell Carcinoma of the Head and Neck who have Failed Standard Platinum-based Chemotherapy. - Zalutumumab in non-curable Patients with SCCHN
• Scientific title: An Open label single arm trial investigating zalutumumab, a Human Monoclonal Anti-EGF receptor Antibody, in combination with Best Supportive Care, in Patients with Non-Curable Squamous Cell Carcinoma of the Head and Neck who have Failed Standard Platinum-based Chemotherapy. - Zalutumumab in non-curable Patients with SCCHN
• Date of first enrolment: 25/11/2008
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000582-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Czech Republic, Germany, Italy, Portugal

Key inclusion & exclusion criteria

Inclusion criteria:
1) Males and females age = 18 years (=19 years of age in countries where patients are required to be so for adult participation in a clinical trial).

2) Histologically or cytologically confirmed diagnosis, initially or at relapse, of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, considered incurable with standard therapy.

3) Failure to at least one course of standard platinum-based chemotherapy.
One course of standard platinum-based chemotherapy is defined as at least two cycles of cisplatin (=60 mg/m2/cycle) or carboplatin (= 250 mg/m2/cycle). The interval between the cycles should be less than or equal to 4 weeks. For other dose-regimens a total accumulative dose of cisplatin =120 mg/m2 or carboplatin = 500 mg/m2 given within a maximum of 8 weeks is acceptable (dose-intensity =15 mg/m2/week for cisplatin and = 62 mg/m2/week for carboplatin).
Platinum-based chemotherapy may have been given as monotherapy, or in combination with other chemotherapy including fluorouracil (5-FU) and/or radiation.
Failure is defined as (a) refractory or (b) intolerant to a standard platinum-based chemotherapy as follows:

a. Refractory is defined as disease progression according to RECIST during one course of standard platinum-based chemotherapy or within 6 months after completion of one course of standard platinum-based chemotherapy, given as treatment of

• non-metastatic disease when platinum-based chemotherapy was given with a curative intention
• metastatic disease
• relapse not amenable for curative intervention

b. Intolerant is defined as discontinuation of one course of platinum-based chemotherapy due to side effects/toxicity irrespective of response

Patients must have disease progression according to RECIST, documented with two CT scans or MR images.
1) If a patient has obtained a response according to RECIST after standard platinum based chemotherapy the patient is eligible if a progression is confirmed within 6 months following standard platinum based chemotherapy.
Disease progression should be documented with:
• a scan/image acquired at response after standard platinum-based chemotherapy or a scan/image acquired before standard platinum based chemotherapy
and
• a scan/image acquired within 6 months after standard platinum based chemotherapy
2) If a patient has obtained no response after platinum based chemotherapy
Disease progression should be documented with
• a scan/image acquired before standard platinum based chemotherapy
and
• a scan/image acquired within 6 months after standard platinum based chemotherapy.
In both situations the scan taken at the screening visit for this trial may serve as the progression scan if it is performed within 6 months after standard platinum based chemotherapy.

4) Measurable disease defined as one or more target lesions according to RECIST.

5) WHO performance status = 2.

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) Three or more prior chemotherapy regimens, other than platinum based chemotherapy

2) Prior treatment with EGFr antibodies and/or EGFr small molecule inhibitors unless given as part of first line treatment of locally or regionally advanced SCCHN in combination with chemotherapy and/or radiotherapy. Exposure to EGFr targeted therapy must be completed =6 weeks prior to visit 2.

3) Received the following treatments within 4 weeks prior to Visit 2:
? Cytotoxic or cytostatic anti-cancer chemotherapy
? Total tumor resection

4) Past or current malignancy other than SCCHN, except for:
? Cervical carcinoma Stage 1B or less
? Non-invasive basal cell and squamous cell skin carcinoma
? Malignant melanoma with a complete response of a duration of > 10 years
? Other cancer diagnoses with a complete response of a duration of > 5 years
? Stage 1 or 2 treated prostate cancer with a prostate specific antigen (PSA) in the normal range for >2 years post treatment.

5) Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, sinusitis, and tuberculosis. Exempted are secondary infections in tumor lesions.

6) Known brain metastasis or leptomeningeal disease.

7) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities

8) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease evaluated by the investigator to interfere with effect of the study drug

9) Expected survival < 3 months.

10) Known HIV positive

11) Known hepatitis B and/or C

12) 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)
? ALP > 2.5 times the upper limit of normal (unless known bone metastases)
? Bilirubin > 1.5 times the upper limit of normal
? Calculated creatinine clearance < 50mL/min

13) Current participation in any other interventional clinical study

14) Patients known or suspected of not being able to comply with this trial protocol

15) Breast feeding women or women with a positive pregnancy test at Visit 1.

16) Women of childbearing potential not willing to use adequate contraception as hormonal birth control, intrauterine device or double barrier method, during study and 12 months after last dose of zalutumumab.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-Curable Squamous Cell Carcinoma of the Head and Neck
MedDRA version: 9.1 Level: LLT Classification code 10060121 Term: Squamous cell carcinoma of head and neck

Intervention(s)

Product Name: Zalutumumab
Product Code: HuMax-EGFr
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Zalutumumab
CAS Number: 667901-13-5
Current Sponsor code: HuMax-EGFr
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: To investigate zalutumumab in combination with BSC with respect to efficacy and safety and to determine the pharmacokinetic profile of zalutumumab.

Main Objective: To investigate zalutumumab in combination with BSC in terms of overall survival in non-curable patients with recurrent and/or metastatic disease who have failed after at least one course of standard-based chemotherapy.

Primary end point(s): Overall Survival (OS) defined as the time from start of treatment until date of death from any cause.

Secondary ID(s)

2008-000582-39-PT

GEN205