A Randomized, Open-label, Multi-center Trial Investigating Zalutumumab, a Human Monoclonal Anti-EGF receptor Antibody, in Combination with Chemo-Radiation in Stage IIIA-IIIB Non Small Cell Lung Cancer Patients - Zalutumumab in Combination with Chemo-Radiation in NSCLC

Phase 1

Conditions: Stage IIIA-IIIB Non Small Cell Lung Cancer
MedDRA version: 8.1Level: LLTClassification code 10029519Term: Non-small cell lung cancer stage III

Registration Number: EUCTR2006-004945-40-NL

Lead Sponsor: Genmab A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 273

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

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. 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 defines 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 > 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 pf 38%.
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 10^9/L, neutrophils < 1.5 x 10^9/L, platelets < 100 x 10^9/L, hemoglobin < 10 g/dL
7. Renal function: creatinine clearance calculated by the Cockcroft and Gault equation < 50
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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: 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.;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

Secondary Outcome Measures

Name	Time	Method

Related Trials