E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III, IVa or IVb Locally Advanced Squamous Cell Carcinoma of the Head and Neck Ineligible for Platinum based Chemotherapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023860 |
E.1.2 | Term | Laryngeal squamous cell carcinoma stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023861 |
E.1.2 | Term | Laryngeal squamous cell carcinoma stage IV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Adverse events (AEs) including skin rash (CTCAE grading, onset, and duration), acute and late radiation toxicities 2) Host immune response: Human Anti Human Antibodies (HAHA)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |