EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer MedDRA version: 18.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: * Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009) * Eligible for first-line treatment with erlotinib based on previously documented evidence of tumor that has EGFR exon 19 deletion or exon 21 (L858R) substitution mutation. * Mandatory provision of adequate archived stage IV NSCLC tissue sample. * At least one or more measurable lesion attributed to NSCLC , documented by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 * Prior radiation therapy is allowed * Adequate hematologic and organ function * Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and for at least 12 weeks after the last dose of study therapy. * Resolution to Grade =1 (except alopecia), by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy. * Life expectancy of at least 3 months and, in the judgment of the investigator, will be able to complete at least 2 cycles of treatment. 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 330 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 220
Exclusion criteria
Exclusion criteria: * Known T790M EGFR mutation * Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases * Major surgery within 28 days or subcutaneous venous access device placement within 7 days prior to enrollment. Any patient with postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months will be excluded * Pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently * Superior vena cava syndrome * Clinically relevant congestive heart failure [NYHA] II-IV; or symptomatic or poorly controlled cardiac arrhythmia * Serious illness or medical condition including Cirrhosis at a level of Child-Pugh Class B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis. Patients with a history of hepatorenal syndrome should also be excluded. * Uncontrolled hypertension * Ongoing treatment with CYP3A4 inducers or strong/moderate inhibitors * Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months or other antiplatelet agents. Aspirin use at doses up to 325 mg/day is permitted * History of gross hemoptysis within 2 months * Significant bleeding disorders, vasculitis, or experienced Grade 3/4 GI bleeding within 3 months * Radiologically documented evidence of major blood vessel invasion or encasement by cancer * Radiographic evidence of intratumor cavitation, regardless of tumor histology * History of gastrointestinal perforation, peptic ulceration, diverticular disease, and/or fistulae within 6 months * History of bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea * History of any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months * The patient has any known significant ophthalmologic abnormalities of the surface of the eye * The patient requires daily use of prescription or over-the-counter proton pump inhibitors * Any prior anticancer therapy for Stage IIIB/IV NSCLC * Any evidence of clinically active interstitial lung disease. Asymptomatic patients with chronic, stable, radiographic changes are eligible * Preexisting idiopathic pulmonary fibrosis as evidenced by CT scan/X-ray at baseline; have or had any disease of acute lung injury, idiopathic pulmonary fibrosis, or pneumoconiosis evident on an X-ray; have or had any disease of radiation pneumonia or drug-induced pneumonia * The patient has SPO2 < 94 (room air)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of Part B is to compare the PFS of ramucirumab administered in combination with erlotinib versus placebo in combination with erlotinib in previously untreated patients with EGFR mutation-positive metastatic NSCLC.;Secondary Objective: Secondary objectives of Part B are to compare ramucirumab administered in combination with erlotinib versus placebo administered in combination with erlotinib for: • safety and toxicity profile • overall survival (OS) • objective response rate (ORR) (complete response [CR] + partial response [PR]) • disease control rate (DCR) (CR + PR + stable disease [SD]) • duration of response (DOR) • pharmacokinetics (PK) and immunogenicity of ramucirumab • patient-reported outcomes (using Lung Cancer Symptom Scale [LCSS] and EuroQol 5 dimension, 5-level questionnaire [EQ 5D-5L]);Primary end point(s): Part B: Progression Free Survival (PFS) ;Timepoint(s) of evaluation of this end point: Part B: After 320 PFS events for approximately 450 patients have been reported. PFS is measured from the date of randomization to the date of radiographic documentation of progression (as defined by RECIST v. 1.1) based on investigator assessment, or the date of death due to any cause, whichever is earlier. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • overall survival (OS) defined as the time from the date of randomization until the date of death from any cause • objective response rate (ORR) (complete response [CR] + partial response [PR]) defined as the proportion of randomized patients achieving a best overall response of PR or CR, from randomization to disease progression. • disease control rate (DCR) (CR + PR + stable disease [SD]) defined as the proportion of randomized patients achieving a best overall response of PR or CR or SD, from randomization to disease progression. • duration of response (DOR) defined from the date of first documented CR or PR (responder) to the date of objective progression or the date of death due to any cause, whichever is earlier. • pharmacokinetics (PK) of ramucirumab: Cmin from Cycle 2 predose through Cycle 14 predose • Number of patients with Anti-Ramucirumab antibodies from Cycle 1 predose through follow-up • Change from baseline on the Lung Cancer Symptom Scale [LCSS] - time to deterioration (TtD) for each of the 9 items • Change from baseline on the EuroQoL 5-dimension, 5-Level Questionnaire (EQ-5D-5L): -Descriptive statistics for the 5 dimensions, index, and VAS calculated for each assessment period • Resource Utilization - Hospitalizations, transfusions, and concomitant medications during the study treatment period or during the 30-day short-term follow-up period;Timepoint(s) of evaluation of this end point: After at least 300 OS events have been reported | — |
Countries
Canada, China, France, Germany, Greece, Hong Kong, Italy, Japan, Korea, Republic of, Spain, Taiwan, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed