Advanced or Metastatic Non Small Cell Lung Cancer MedDRA version: 9.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS
Conditions
Sponsors
Eli Lilly and Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Histologic or cytologic diagnosis of NSCLC with locally advanced or metastatic disease (Stage IIIA, IIIB or IV at entry) that is not amenable to curative therapy per the American Joint Committee on Cancer Staging Criteria for lung cancer. [2] Patients must have progressive disease after 1 prior systemic cytotoxic chemotherapy regimen for advanced disease. Prior chemotherapy given as neoadjuvant or adjuvant therapy for early stage disease, completed at least 12 months prior to the diagnosis of advanced stage disease, will not be counted as a prior regimen. Previous treatment with bevacizumab or other targeted agent is permitted, provided that the targeted agent was initiated concurrently with chemotherapy as part of first line treatment. [3] At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines. [4] Performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) performance status scale. [5] Discontinuation of all previous systemic therapies for cancer (including targeted agents such as bevacizumab) for at least 2 weeks prior to enrollment. The patient must have recovered from all acute toxic effects of the therapies. [6] Previous radiation therapy (including thoracic radiation) allowed to 25% of the bone marrow, but should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to enrollment (except for alopecia). Prior radiotherapy must be completed at least 2 weeks prior to enrollment. Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy. [7] Estimated life expectancy of at least 8 weeks. [8] Compliance and geographic proximity that allow adequate follow-up. [9] Adequate organ function including the following: • Adequate bone marrow reserve: white blood cell (WBC) count = 3.0 x 109/L, absolute neutrophil count (ANC) =1.5 x 109/L, platelet count = 100.0 x 109/L and hemoglobin = 9.0 g/dL (=5.6 mmol/L). • Hepatic: bilirubin =1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT)=2.5 x ULN, or = 5 x ULN with liver metastases. • Renal: serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [13] Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [14] Previous treatment with enzastaurin or pemetrexed. [15] Recent (within 30 days of enrollment) or concurrent yellow fever vaccination. [16] Serious concomitant systemic disorder (for example, active infection) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. [17] Serious cardiac condition, such as myocardial infarction within 6 months, angina, abnormal ECG indicative of cardiac disease, or heart disease, as defined by the New York Heart Association Class III or IV. Patients with a QTc prolongation > 450 msec (males) or > 470 msec (females) and patients who have a congenital long-QT syndrome in their own medical history or family medical history should be excluded. [18] Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. [19] Central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before study enrollment). A screening computed tomography (CT) or magnetic resonance imaging (MRI) scan before enrollment, in the absence of a clinical suspicion of brain metastases, is not required. [20] Concurrent administration of any other antitumor therapy. [21] Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study enrollment. [22] Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose = 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). [23] Inability or unwillingness to take folic acid or vitamin B12 supplementation. [24] Inability to take corticosteroids. [25] Unable to swallow tablets. [26] Unable to discontinue use of carbamazepine, phenobarbital, and phenytoin. [27] Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare pemetrexed plus enzastaurin when given in a twice daily dosing schedule versus pemetrexed plus placebo twice daily in terms of the progression-free survival time (PFS) of patients receiving second-line therapy for the treatment of locally advanced or metastatic NSCLC. ;Secondary Objective: To assess and compare the following variables between treatment arms: • time-to-event variables, including: ? overall survival (OS) ? time to worsening of symptoms (TWS) ? duration of disease control (DDC) • disease control (best response of stable disease [SD], partial response [PR], or complete response [CR]) • tumor response (best response of partial response [PR], or complete response [CR]) • the safety and adverse event profile (including Common Terminology Criteria for Adverse Events [CTCAE v3.0, NCI 2006] grades for laboratory and nonlaboratory adverse events) • maximum improvement over baseline score for each item of the Lung Cancer Symptom Scale (LCSS). • biomarkers relevant to enzastaurin, pemetrexed, and the disease state, as well as their correlation to clinical outcome. ;Primary end point(s): Progression Free Survival time | — |
Countries
France, Germany, Italy, Portugal
Outcome results
None listed