A study of erlotinib (Tarceva®) treatment in patients with locally advanced or metastatic non-small cell lunf cancer who present activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor

• Conditions: ocally advanced or metastatic non-small cell lung cancer with activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor.; MedDRA version: 14.0Level: LLTClassification code 10025054Term: Lung cancer non-small cell stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2010-023869-21-FI
• Lead Sponsor: Roche Oy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-22
• Last Update Posted: 23 December 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

1. Patients able and willing to give written informed consent. Consent must be obtained prior to any study-specific procedure.
2. Histologically or cytologically documented inoperable, locally advanced (inoperable and not eligible for chemoradiotherapy stage IIIB) or metastatic (stage IV) NSCLC disease who present activating mutations (exon 19 deletions or exon 21 substitution L858R) in the tyrosine kinase domain of EGFR.
3. Measurable disease must be characterized according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria or according to standard of care.
4. Male or female patients aged = 18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
6. Life expectancy = 12 weeks.
7. Adequate hematological function: Absolute neutrophil count (ANC) = 1.5 x 109/L, and Platelet count = 100 x 109/L, and Hemoglobin = 9 g/dL (may be transfused to maintain or exceed this level).
8. Adequate liver function: Total bilirubin < 1.5 x upper limit of normal (ULN), and aspartate aminotransferase (ASAT) and/or alanine aminotransferase (ALAT) < 2.5 x ULN in patients without liver metastases; < 5 x ULN in patients with liver metastases.
9. Adequate renal function: Serum creatinine = 1.25 x ULN.
10. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
11. Female patients must be postmenopausal (24 months of amenorrhea), surgically sterile or they must agree to use a physical method of contraception. Male patients must be surgically sterile or agree to use a barrier method of contraception. Women with an intact uterus must have a negative pregnancy test (urine or serum) if clinically warranted.
12. Patients with asymptomatic and stable cerebral metastases receiving medical treatment will be eligible for the study. Those patients may have received radiation therapy for their cerebral metastases before the initiation of systemic treatment for non-small-cell lung cancer also will be eligible.
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. Previous treatment with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor) for metastatic disease. The administration of neoadjuvant or adjuvant therapy is allowed as long as it has finalized ³ 6 months before entering the study. Patients can have received radiotherapy as long as the irradiated lesion is not the only target lesion for evaluating response and as long as radiotherapy has been completed before initiating the study treatment (a 2-week period is recommended).
2. Treatment with an investigational drug agent during the 3 weeks before enrollment in the study.
3. History of another neoplasm other than carcinoma in situ of the uterine cervix, basal cell skin carcinoma treated adequately, or prostate carcinoma with a good prognosis (Gleason £ 6) treated radically. History of another neoplasm treated curatively and without evidence of disease in the last 5 years.
4. Patients with symptomatic cerebral metastases.
5. Known hypersensitivity to erlotinib or any of its excipients.
6. Any significant ophthalmologic abnormality, especially severe dry eye syndrome,
keratoconjunctivitis sicca, Sjögrens syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions. The use of contact lenses is not recommended during the study. The decision to continue to wear contact lenses should be discussed with the patient’s treating oncologist and the ophthalmologist.
7. Coumarins (CoumadinTM; warfarin) use. If the patient requires anti-coagulation therapy, the use of low molecular weight heparin instead of coumarins is recommended where clinically possible.
8. Unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
9. Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
10. Patients with pre-existing parenchymal lung disease such as pulmonary fibrosis.
11. Patients with known infection with HIV, HBV, HCV. Testing is not required in the absence of clinical signs and symptoms suggestive of these conditions.
12. Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
13. Incapacity to take oral medication or previous surgical procedures that affect absorption and imply the need for intravenous or parenteral feeding.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy of erlotinib (TarcevaTM; 150 mg) on<br>progression-free survival (PFS) in patients with<br>non-small-cell lung cancer (NSCLC) in locally<br>advanced or metastatic stages (stage IIIB and stage<br>IV) who have not received previous chemotherapy<br>for their disease and who present activating<br>mutations in the tyrosine kinase (TK) domain of the<br>epidermal growth factor receptor (EGFR).;Secondary Objective: Investigator assessed objective response<br>· Safety profile<br>· Overall survival (OS)<br>· The rate of EGFR mutations in patients with NSCLC in Finland;Primary end point(s): PFS, defined as the time from the first dose of erlotinib to the date of first occurrence of disease progression or death.