Lung cancer is one of the most common malignancies in developed countries and accounts for millions of deaths worldwide. Two-thirds of NSCLC patients have advanced disease and are considered incurable by surgery or chest radiation. The current standard of care for these patients is chemotherapy. Novel therapeutic agents are under development. Epidermal growth factor inhibitors have already demonstrated a clinical benefit to patients with advanced NSCLC failing standard chemotherapy regimens. M
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with advanced NSCLC (unresectable or metastatic) • Age = 18 years old • Pathologic confirmation of NSCLC • Tumor tissue samples (paraffin block or unstained slides) must be available for central analysis of molecular markers for those patients entered on the Phase 2 part of the study. If possible, tumor tissue samples should be available for patients enrolled in Phase 1 part of the study • Patients entered on the phase 2 of the study must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. • Patients must have been treated with chemotherapy for advanced disease and have documented tumor progression (serial CT scans demonstrating progressive disease according to RECIST must be available) despite = 2 chemotherapy schedules for treatment of advanced disease (previous therapy for localized disease is not counted), one of which must have included cisplatin or carboplatin • More than two weeks since any major surgery, completion of radiation, or completion of all prior chemotherapy (adequately recovered from the acute toxicities of any prior therapy) • WHO performance status £ 2 • Adequate bone marrow function as shown by: ANC = 1.5 x 109/L, Platelets = 100 x 109/L, Hgb > 9 g/dL • Adequate liver function as shown by serum: bilirubin = grade 2 and transaminases activity = 3 x ULN. With the exception of serum transaminases (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients will be excluded if they meet ANY of the following criteria: • Concurrent therapy with agents otherwise used in treatment of cancer (for example, methotrexate for rheumatoid arthritis) • Treatment with any other investigational drugs within the preceding 4 weeks • Prior treatment with an EGFR inhibitor (either a small molecule EGFR TK inhibitor or ant-EGFR antibody) • Chronic treatment with steroids or another immunosuppressive agent • Leptomeningeal or uncontrolled brain metastases, including patients who continue to require glucocorticoids or intrathecal chemotherapy for brain or leptomeningeal metastases (documented by lumbar puncture) • Malignancies other than lung cancer within the past 2 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. • Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration) • A known history of HIV or previous seropositivity for the virus • Patients with active skin, mucosa, ocular or GI disorders of grade > 1 • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 or erlotinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin) • Women who are pregnant or breast feeding, or women able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001 or erlotinib) • History of noncompliance to medical regimens • Patients unwilling to or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the value of combined treatment with RAD001 and erlotinib in patients with advanced NSCLC previously treated only with chemotherapy as systemic therapy. The study consists of two consecutive phases, the primary aims of which are: Phase 1: To assess the feasibility (in terms of both dose and schedule) of combined daily or weekly administration of RAD001 with daily erlotinib based on evaluation of safety and PK drug-drug interaction and to establish the appropriate doses to carry forward into phase 2. In phase 2: To assess the antitumor activity of RAD001 and erlotinib combination schedule (or schedules, depending on the outcome of phase 1), based on the evaluation of the objective response rate (ORR) and early progression rate (EPR) ;Secondary Objective: In phase 1: • To assess the clinical efficacy of RAD001 and erlotinib combination schedule, based on evaluation of ORR and EPR • To investigate potential molecular markers In phase 2 • To assess the safety of combined administration of RAD001 and erlotinib • To assess steady state drug levels • To investigate potential molecular markers;Primary end point(s): Phase 1: assess feasibility (in terms of dose and regimen) based upon safety and pharmacokinetic drug-drug interaction Phase 2: objective response rate and rate of early disease progression | — |
Countries
Denmark, France
Outcome results
None listed