E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIA-IIIB Non Small Cell Lung Cancer |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
|
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 demonstrate that treatment with zalutumumab in combination with chemo-radiation is superior to chemo-radiation alone in terms of progression free survival in treatment naïve stage IIIA–IIIB NSCLC patients. |
|
E.2.2 | Secondary objectives of the trial |
To investigate zalutumumab in combination with radiotherapy and in combination with chemo-radiation therapy with respect to safety and efficacy, to evaluate if gene copy number has a value as prognostic factor as well as being a biomarker for response to zalutumumab, and to determine the pharmacokinetic profile of zalutumumab in stage IIIA-IIIB NSCLC patients. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological or cytological diagnosis of NSCLC in one of the following subtypes: Squamous cell carcinoma, basaloid carcinoma, adenocarcinoma, adenosquamous carcinoma, large cell carcinoma, large cell neuroendocrine carcinoma, giant cell carcinoma, sarcomatoid carcinoma and non small cell carcinoma NOS 2. Any stage III NSCLC based on CT scan, due to invasion or involvement of mediastinal structures or lymph nodes. In the latter case, proof of nodal status involvement should be confirmed either by cytology or histology, or by appropriate PET imaging (for definition of nodal status, see section 20.2, Definition of Terms) 3. Performance status 0 or 1 (Zubrod or WHO Scale) 4. Age ≥ 18 years 5. Following receipt of verbal and written information about the trial, the patient has provided signed informed consent before any trial related activity is carried out
|
|
E.4 | Principal exclusion criteria |
1. Evidence of metastases (based on whole body PET scan and CT scan or MRI of brain), either in a separate lobe of the lung, or extra thoracic 2. Malignant pleural effusion defined as any significant pleural effusion that has been proven cytologically positive. Non-malignant pleural effusions need to be negative on at least 2 punctures with cytological examination and/or thoracoscopy. 3. Eligible patients should have tumor volumes that are unlikely to result in a high risk of radiation pneumonitis, and high-risk will be defined as the need to use fields that are likely to result in a V20 of greater than 35%. If a patient who has been included is subsequently found to have a V20 of > 35%, this patient will remain eligible unless the V20 is in excess of 38%. The volume of normal lung which is included in the GTV is not included in the V20 calculation. 4. Estimated life expectancy of less than 3 months 5. Unwillingness and inability to attend the required follow-up 6.Bone marrow reserve: white blood cell count (WBC) < 3.0 x 109/L, neutrophils < 1.5 x 109/L, platelets < 100 x 109/L, hemoglobin < 10 g/dL = 6.2 mmol/L. 7.Renal function: creatinine clearance calculated by the Cockcroft and Gault equation < 50 mol/L. 8. Liver function: bilirubin > 1.5 x normal. ALT, alkaline phosphatase and AST > 2.5 x normal 9. Impaired respiratory function as indicated by a forced expiratory volume in 1 second (FEV1) of less than, or equal to, 40% of predicted normal values OR a diffusion capacity for carbon monoxide (DLCO) of less than, or equal to, 50% of predicted normal values (based on measurement of both parameters) 10. Evidence of malignancy in the past 2 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other in situ cancers 11. History of interstitial pneumonitis 12. Severe COPD requiring ≥ 3 hospitalizations over the past year 13. Peripheral neuropathy > grade 1 14. Unintended weight loss of ≥ 15% in the 3 months prior to enrolment 15. Chronic or current infectious disease such as, but not limited to, chronic renal infection, sinusitis, tuberculosis, and chronic chest infection with bronchiectasis 16. Severe ongoing infection requiring intravenous antibiotic or antifungal therapy 17. Serious concomitant systemic disorder incompatible with the trial 18. Known HIV positive 19. Known hepatitis B or hepatitis C 20. Prior chemotherapy for lung cancer 21. Prior radiotherapy to the chest 22. Prior surgery with curative intent for lung cancer 23. Previous exposure to EGFr monoclonal antibodies and/or small molecule inhibitors of EGFr 24. Use of any anti-cancer or investigational agent in the 4 weeks immediately prior to screening 25. Current participation in any other interventional clinical trial 26. Breast feeding women or women with a positive pregnancy test at Visit 1 27. Male not willing to use adequate contraception during and for 12 months after last dose of zalutumumab or woman of childbearing potential not willing to use adequate contraception such as hormonal birth control or intrauterine device, during trial and 12 months after last dose of zalutumumab. For patients in the USA the use of a double barrier method is also considered adequate.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) defined as the time from randomization until disease progression (verified by imaging technique and according to RECIST) or death |
|
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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Chemotherapy in combination with radiotherapy |
|
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |