Furthermore, meropenem the combination Moxifloxacin clinical trial of enzastaurin plus pemetrexed was well tolerated and showed preliminary evidence of anti cancer activity. Of note, pharmacokinetic parameters of the two drugs were not altered when given in combination . On the basis of these safety and pharmacokinetic data, the recommended dose of enzastaurin in combination with chemotherapy is 500 mg QD. This study was designed in two parts to evaluate whether enzastaurin 250 mg BID can provide additional benefit when combined with cisplatin pemetrexed. As this was the first clinical evaluation of this combination, patients first entered a single arm, open label, lead in phase to evaluate the safety of enzastaurin in combination with cisplatin pemetrexed.
A subsequent multicenter, randomized, double blind, placebo controlled phase II study evaluated the efficacy and safety of enzastaurin plus cisplatin pemetrexed compared with cis platin pemetrexed plus placebo in non squamous NSCLC. Methods Eligibility Criteria Patients included Moxifloxacin structure in the study had no prior systemic chemotherapy, a performance status of 0 or 1, a histologic/cytologic diagnosis of advanced NSCLC , measurable disease according to Response Evaluation Criteria in Solid Tumors , prior radiation to ! 25% of bone marrow, and adequate organ function. Patients were excluded from the study for central nervous system metastases, myocardial infarction ! 6 months before enrollment, significant cardiac abnormalities, peripheral neuropathy grade 6 2, or the inability to interrupt the use of high dose aspirin or other non steroidal anti inflammatory drugs.
The protocol was approved Moxifloxacin solubility by the ethical review board of each participating institution. Written informed consent was obtained from each patient before enrollment. The study was conducted according to the ethical principles of the Declaration of Helsinki and Good Clinical Practices and applicable laws and regulations. Study Design and Treatment The first part of this study was a single arm, open label, safety lead in phase of enzastaurin plus cisplatin pemetrexed that was designed to evaluate the toxicity of two doses of enzastautin in two patient cohorts plus standard doses of cisplatinpemetrexed. Since the differential effects of pemetrexed due to histology were not known at the time the study began, and because no differences in safety as a function of histology were anticipated in this study, patients with any NSCLC histology were eligible to participate in the safety lead in phase.
For each cohort, patient safety was evaluated during cycle 1, and if no adverse events beyond the expected safety profile of cisplatin pemetrexed occurred in cycle 1, then the study moved forward. A subsequent randomized, double blind, placebo controlled phase was to evaluate the efficacy and safety of the combination compared with cis platin pemetrexed in non squamous NSCLC. All patients welfare state received folic acid, vitamin B 12 supplementation, and dexamethasone prophylaxis. In cohort 1, patients received enzastaurin 125 mg postoperatively BID with pemetrexed 500 mg/m 2 intravenously, then cisplatin 75 mg/m 2 . Patients in cohort 2 were to receive the same regimen as in cohort 1 but with enzastaurin 250 mg PO BID after a 375 mg loading dose three times a day.