Phase II, open-label study of erlotinib (Tarceva®) treatment in patients with locally advanced or metastatic non-small cell lung cancer who present activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor. - MuTAR
- Conditions
- Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC who have not received previous chemotherapy for their disease and who present activating mutations in the TK domain of the EGFR.Any patient with locally advanced or metastatic non-small cell lung cancer disease found to have an EGFR Exon 19 deletion or exon 21 substitution L858R in the TK domain of EGFR gene will be offered first-line treatment with erlotinib.
- Registration Number
- EUCTR2010-022509-17-PT
- Lead Sponsor
- Roche Farmacêutica Química, Lda
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
1.Patients able and willing to give written informed consent. Consent must be obtained prior to any study-specific procedure.
2.a) Histologically or cytologically documented inoperable, locally advanced or metastatic NSCLC disease;
2.b) Patient that presents activating mutations (exon 19 deletion and/or exon 21 substitution L858R ) in the tyrosine kinase domain of EGFR ;
3.Measurable disease, according to RECIST - Response Evaluation Criteria in Solid Tumours).
4.Male or female patients aged = 18 years.
5.Life expectancy = 12 weeks.
6.Adequate haematological and coagulation function as assessed by the investigator.
7.Adequate liver and renal function as assessed by the investigator.
8.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. Male and female patients must use effective contraception during the study and for a period of 90 days following the last administration of erlotinib. Acceptable methods of contraception include an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms) with spermicidal.
9.If applicable, 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.
10.Able to comply with the required protocol and follow-up procedures.
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
1.Previous treatment with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor) for metastatic disease. The administration of neo-adjuvant or adjuvant therapy is allowed as long as it has finalized 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 (28 days period is recommended). Treatment with an investigational drug agent during the four weeks before enrolment in the study.
2.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. History of breast cancer and melanoma at any time.
3.Patients with symptomatic cerebral metastases.
4.Known hypersensitivity to erlotinib or any of its excipients.
5.Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren’s 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.)
6.Use of coumarins (Sintrom®; Varfine®). If the patient requires anti-coagulant therapy, instead of coumarins, the use of a low molecular weight heparin is recommended, whenever clinically possible.
7.Patients with severe hepatic and renal impairment as assessed by the investigator.
8.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.
9.a) Positive urine/blood pregnancy test in women of childbearing potential. Female patients should not be pregnant or breast-feeding.
9.b) Patients (male or female) with reproductive potential not willing to use effective method of contraception during the trial and during 90 days after the last erlotinib administration. Oral or injectable contraceptive agents cannot be the sole method of contraception.
10.Patients with pre-existing disease of the lung parenchyma such as lung fibrosis, lymphangitic carcinomatosis.
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 those in the Investigator’s opinion are not able to accomplish protocol requirements.
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 Primary end point(s): The primary efficacy endpoint is ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR), as per RECIST 1.1, is observed, assessed based on diagnostic imaging. <br>;Main Objective: To evaluate the objective response rate (ORR) of erlotinib (Tarceva®; 150 mg) in patients with locally advanced or metastatic stage non-small-cell lung cancer (NSCLC), who have not received previous chemotherapy for their disease and who present activating mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR).;Secondary Objective: To evaluate the Progression-free survival (PFS);<br>To evaluate the Overall Survival defined as the time from baseline visit to the date of death due to any cause;<br>To evaluate the erlotinib safety profile (Tarceva®; 150 mg);<br>To evaluate the EGFR mutation frequency, in the study population.<br>To evaluate the Response Duration (RD).<br><br>
- Secondary Outcome Measures
Name Time Method