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
Lilly S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: * The patient has 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) * The patient must be 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. * The patient has 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. * The patient has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 * Prior radiation therapy is allowed * The patient has 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. * The patient has 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. * The patient has a 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: * The patient has known T790M EGFR mutation * The patient has known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases * The patient has undergone 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 * The patient has pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently * The patient has superior vna cava syndrome * The patient has clinically relevant congestive heart failure [NYHA] II-IV; or symptomatic or poorly controlled cardiac arrhythmia * The patient has a 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. * The patient has uncontrolled hypertension * The patient is being treated with CYP3A4 inducers or strong/moderate inhibitors * The patient is receiving 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 * The patient has a history of gross hemoptysis within 2 months * The patient has significant bleeding disorders, vasculitis, or experienced Grade 3/4 GI bleeding within 3 months * The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer * The patient has radiographic evidence of intratumor cavitation, regardless of tumor histology * The patient has a history of GI perforation, peptic ulceration, diverticular disease, and/or fistulae within 6 months * The patient has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea * The patient has experienced 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 * The patient had any prior anticancer therapy for Stage IIIB/IV NSCLC * The patient has any evidence of clinically active interstitial lung disease. Asymptomatic patients with chronic, stable, radiographic changes are eligible * The patient has 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 study is divided into 2 parts. Part A is the Phase 1b portion of the trial and Part B is the Phase 3 portion of the trial. Once the Assessment Committee (AC) has completed the DLT assessment for Part A, the outcome of those results will confirm the Part B dose and Part B enrollment will proceed. The objective(s) for each part are as follows: Part A: The objective of Part A is to assess the safety and tolerability of ramucirumab when administered in combination with erlotinib as therapy in previously untreated patients with EGFR mutation-positive metastatic NSCLC. Part B: 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]) There are no secondary objectives planned for Part A in this study.;Primary end point(s): Part A: single arm to determine the recommended dose for Phase 3 part. Two cohorts of patients will be enrolled to assess the safety and tolerability of ?ramucirumab 10 mg/kg q2w + erlotinib 150 mg daily?. Part B: Progression Free Survival (PFS);Timepoint(s) of evaluation of this end point: Part A completion is considered when the DLT assessment has been completed. Part B: After 320 PFS events for approximately 450 patients have been reported. PFS is measured from | — |
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 and concentrations at 1 hour post end of infusion (approximately maximum concentration [Cmax]) ? Number of patients with Anti-Ramucirumab antibodies - Correlation to ramucirumab drug level, activity, and safety ? 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, Hong Kong, Japan, Korea, Republic of, Spain, Taiwan, United States
Contacts
Public ContactMaria José Hernandez
Lilly S.A.
Outcome results
None listed