Non-small-cell-lung-cancer MedDRA version: 9.1 Level: LLT Classification code 10066490 Term: Progression of non small cell lung cancer
Conditions
Interventions
Product Name: Tarceva
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: erlotinib
CAS Number: 183319-69-9
Current Sponsor code: Ro 50-8231 / OSI-774
Concentration unit: mg milligram(s)
Conc
Sponsors
Genentech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible for this second-line therapy study if they have recurrent or refractory (progression through at least two cycles of a given chemotherapeutic regimen) NSCLC following standard first-line chemotherapy or chemoradiotherapy. • Signed written informed consent • Cytologically or histologically confirmed NSCLC Patients had to have histologically or cytologically confirmed NSCLC. Tumors of mixed histology were categorized by the predominant cell type unless small cell elements were present, in which case the patient was not eligible for study participation. Cytologic or histologic elements have been established on metastatic tumor aspirates or biopsy. Patients with squamous cell carcinoma were eligible provided that their disease was extrathoracic or that their intrathoracic disease consists of peripheral lesions only. A peripheral lesion was defined as a lesion (or lesions) in which the epicenter of the tumor was = 2 cm from the costal or diaphragmatic pleura in a 3-dimensional orientation based on each lobe of the lung, and > 2 cm from the trachea, main, and lobar bronchi. Squamous cell carcinoma patients were eligible for study participation irrespective of the proximity of their adenopathy to the costal or diaphragmatic pleura or major airways. Patients with hilar adenopathy were eligible for study participation. Patients with squamous cell carcinoma had to have a copy of the screening computed tomography (CT) or magnetic resonance imaging (MRI) scans (either as copy films or digital images) reviewed by Genentech or its designee prior to randomization. Patients were not randomized until Genentech or its designee confirmed eligibility. Patients with a history of brain metastases were eligible for study participation, as long as their brain metastases had been treated and they did not have an ongoing requirement for treatment with dexamethasone at screening. Treatment had to be with WBRT (e.g., 3000 cGy over 2 weeks) and might include neurosurgery, or stereotactic radiosurgery. Radiotherapy and stereotactic radiosurgery had to be completed at least 4 weeks prior to Day 0 (see Section 4.3.2). Neurosurgery had to be completed at least 24 weeks prior to Day 0, and brain biopsy must be completed at least 12 weeks prior to Day 0. • Clinical or radiographic progression during or after first-line chemotherapy or chemoradiotherapy for NSCLC. Patients receiving neo-adjuvant and adjuvant therapy for Stage I–IIIa disease prior to their first-line regimen were eligible for study participation provided they had also received first-line therapy (for unresectable, metastatic disease) and had demonstrated progression during or after that first-line therapy. • Consent to provide archival tissue for analysis was required for participation in this study. Patients who consented to provide tissue but whose archival tissue was found to be inadequate (e.g., stained slides) remained eligible for study participation. • ECOG performance status of 0, 1, or 2. • Age = 18 years • Use of an acceptable means of contraception for men and women of childbearing potential • INR no greater than 1.3 and an aPTT no greater than the upper limits of normal within 28 days prior to enrollment for patients not on low-molecular-weight heparin or fondaparinux. Patients on low-molecular-weight heparin or fondaparinux were not required to meet INR or aPTT limits. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) y
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria were ineligible for study entry: • Squamous cell carcinoma, except for patients with no intrathoracic disease or small peripheral lesions only. • Prior treatment with an investigational or marketed inhibitor of the EGFR pathway or anti-angiogenesis agent Angiogenesis inhibitors include (but are not limited to) bevacizumab, thalidomide, CP 547632, SU 11248, and PTK 787. • Systemic chemotherapy, radiotherapy, or investigational treatment within 28 days prior to randomization. Local palliative radiotherapy within 14 days prior to randomization or persistent adverse effects from radiotherapy that have not resolved to Grade 2 or less following completion of treatment • Whole brain radiotherapy or stereotactic radiosurgery for brain metastases within 4 weeks of Day 0 • Neurosurgery for brain metastases within 24 weeks of Day 0 • Brain biopsy within 12 weeks of Day 0 • Current use of dexamethasone for treatment associated with brain metastases • History of gross hemoptysis (defined as bright red blood of at least 1/2 teaspoon or 2.5 mL per episode) within 3 months prior to randomization unless definitively treated with surgery or radiation • History of any of the following within 6 months prior to Day 0: serious systemic disease, including myocardial infarction, uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg taken per the JNC 7 guidelines, unstable angina, New York Heart Association (NYHA) Grade 2 or greater CHF, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess. Patients with evidence of hypertension during study screening were to be evaluated for uncontrolled hypertension in accordance with the JNC 7 guidelines. • Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization • CNS bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months • Progressive neurologic symptoms in patients with a history of brain metastases • Full-dose anticoagulation with warfarin. Patients who required full-dose anticoagulation could be treated with low-molecular-weight heparin or fondaparinux. Patients fully anticoagulated with warfarin during the study were discontinued from bevacizumab/placebo. • Chronic daily use of aspirin (> 325 mg/day) or other full-dose NSAIDs with anti-platelet activity. Treatment with other antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, and/or cilostazol) was permitted. • In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization (placement of a central line is not considered surgery, and could be placed on the same day as study drug administration) • Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization • Anticipation of need for a major surgical procedure during the course of the study • Serious, non-healing wound, ulcer, or bone fracture • Inability to take oral medication or requirement for IV alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption • Any of the following abnormal hematologic value
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this Phase III study was to evaluate the efficacy of combining bevacizumab with Tarceva (erlotinib) relative to Tarceva monotherapy in patients receiving second-line therapy for advanced NSCLC. Efficacy will be assessed by measuring overall survival.;Secondary Objective: •Evaluate the safety of combining bevacizumab with Tarceva in patients with previously treated advanced NSCLC, including patients with squamous cell carcinoma, treated brain metastases, and patients receiving full-dose anticoagulation with low-molecular-weight heparin or fondaparinux. •Evaluate the efficacy of combining bevacizumab with Tarceva relative to Tarceva monotherapy in patients with previously treated advanced NSCLC, as measured by PFS, objective response rate, disease control rate and duration of response •Evaluate the pharmacokinetic behavior of Tarceva and the combination of bevacizumab with Tarceva in a subset of patients with previously treated advanced NSCLC •Evaluate the association of survival, PFS, and treatment effect with markers of EGFR expression, as measured by immunohistochemistry (IHC), EGFR gene copy number measured by fluorescence in situ hybridization (FISH) and other molecular markers of EGFR pathway activity in archival tissue samples;Primary end point(s): The primary efficacy endpoint was overall survival, defined as the period from the date of randomization (as entered in the IVRS) until the date of patient death from any cause. All deaths were included, regardless of whether they occur during treatment or following treatment discontinuation. For patients who have not died, survival data were censored at the date of last contact. The two-sided log-rank test, stratified by the randomization stratification factors, was used to perform hypothesis testing for assessing the primary study objective. The randomization stratification factors were ECOG performance status (0/1 vs. 2), smoking history (never vs. current/previous), sex (m | — |
Countries
Bulgaria, Germany, Italy, Sweden
Outcome results
None listed