Trial of BIBW 2992 (afatinib) + Cetuximab in Non-Small Cell Lung Cancer

• Conditions: on-small cell lung cancer patients who developed acquired resistance to Epidermal Growth Factor Receptor - Tyrosine Kinase Inhibitor (EGFR-TKI) following prior treatment with erlotinib or gefitinib or BIBW 2992; MedDRA version: 14.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-015911-42-NL
• Lead Sponsor: Boehringer Ingelheim bv

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-30
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 283

Inclusion Criteria

1.Pathologically or cytologically confirmed Stage IIIB/IV disease or recurrent disease following locoregional treatment
2.Either or both of the following:
•A tumor which harbors an EGFR-mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery. A tumor which harbors exon 20 insertion or de novo T790M mutation is eligible for the treatment in the sequential arm
•Objective clinical benefit from treatment with an EGFR TKI as defined by either
1) Documented partial or complete response (RECIST), or
2) Stable disease =6 months as defined by RECIST in absence of radiographic progression after initiation of gefitinib or erlotinib; or stable disease/PR/CR = 12 weeks as defined by RECIST after initiation of BIBW 2992
3.Systemic progression of disease (RECIST v1.1) while on continuous treatment with erlotinib or gefitinib or BIBW 2992 within the last 30 days. Patients whose disease progresses only in the central nervous system (CNS) are not eligible
4.No intervening systemic therapy between cessation of gefitinib or erlotinib or BIBW 2992 and initiation of the treatment in the study
5.Adequate tumor-derived material such as fresh or archived tumor tissue or pleural fluid from malignant pleural effusion after disease progression on erlotinib/gefitinib/BIBW 2992 must be made available for EGFR mutation analyses
6.Patients aged 18 years or older
7.Life expectancy of at least three (3) months
8.Eastern Cooperative Oncology Group (ECOG) performance score 0-2
9.Written informed consent that is consistent with ICH-GCP guidelines

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 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

Exclusion Criteria

1.Prior treatment with EGFR targeting antibodies
2.Prior severe infusion reaction to a monoclonal antibody
3.Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment
4.Radiotherapy less than two weeks prior to the start of the study treatment
5.Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib/gefitinib/BIBW 2992) <=30 days before study treatment
6. Less than three days from prior treatment with gefitinib or erlotinib. Patients with adverse events related to gefitinib or erlotinb must recover to CTC AE grade 1 or less to be eligible. No need to stop BIBW 2992 before start of the study treatment for patient who progressed on BIBW 2992 from a seperate clinical trial/treatment setting
7.Brain metastases, which are symptomatic. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks. Anticonvulsant therapy will be allowed if patient is stable on anticonvulsant treatment without adjustments of the latter
8.Other malignancies diagnosed within the past five (5) years (other than non melanomatous skin cancer, ductal carcinoma in situ and in situ cervical cancer), unless treated with curative intent. Patients with inactive malignancy may be eligible upon discussion and agreement between investigator and sponsor
9.Known pre-existing interstitial lung disease
10.Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn’s disease, malabsorption, or CTCAE grade >2 diarrhea of any etiology
11.History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, New York Heart Association (NYHA) functional classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 month prior to the study entry
12.Cardiac left ventricular function with resting ejection fraction of less than 50%
13.Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety and anti-tumor activity of the test drug
14.Absolute neutrophil count (ANC) <1000/mm3
15.Platelet count <75,000/mm3
16.Bilirubin >1.5 times upper limit of normal. Aspartate amino transferase (AST) or alanine amino transferase (ALT) >three times the upper limit of normal (if related to liver metastases >five times the upper limit of normal)
17.Serum creatinine >1.5 times of the upper normal limit or calculated/measured creatinine clearance <60 ml/min
18.Known hepatitis B infection, active hepatitis C infection or known HIV carrier
19.Women of childbearing potential (WOCBP), or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial.
20.Pregnancy or breast-feeding
21.Patients unable to comply with the protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified