A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

Eli Lilly and Company41 enrolled

Overview

The purpose of this study is to determine a recommended Phase 2 dose and dosing regimen of LY2090314 in combination with pemetrexed and carboplatin in patients with advanced/metastatic cancer. Part A of this study will consist of dose escalation of the study regimen, and Part B will consist of an expanded cohort to confirm the dose provided from Part A.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Cancer

Interventions

LY2090314DRUG

Administered intravenously

pemetrexedDRUG

Administered intravenously

CarboplatinDRUG

Administered intravenously

ranitidine

Eligibility

Sex: ALLMin age: 25 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale * Have a life expectancy of greater than or equal to 12 weeks * Males and females with reproductive potential agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug * Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease for which no proven effective therapy exists * Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) * Have adequate hematologic, hepatic, and renal function * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Exclusion Criteria: * Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication * Have serious preexisting medical conditions (left to discretion of investigator) * Have one of the following conduction abnormalities: Corrected time between start of Q wave and end of T wave (QTc) prolongation \>450 millisecond (msec) on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long-QT-syndrome, or left bundle branch block (LBBB) * Are taking any concomitant medication that may cause QTc prolongation, or induce Torsades de Pointes * Have systolic blood pressure greater than or equal to 140 millimeters of Mercury (mm Hg), and diastolic blood pressure greater than or equal to 90 mm Hg that is not controlled by medical therapy * Have serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class II or higher; have history of arrhythmia that is symptomatic or requires treatment * Have chronic atrial fibrillation and/or bradycardia * Have uncorrected electrolyte disorders including potassium \<3.4 molar equivalent per liter (mEq/L) (\<3.4 millimole per liter \[mmol/l\]), calcium \<8.4 milligram per deciliter (mg/dL) (2.1 mmol/L), or magnesium \<1.2 mg/dL (\<0.62 mmol/L) * Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required) * Have a hematologic malignancy * Females who are pregnant or lactating

Locations (2)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Tampa, Florida, United States

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD])

Recommended Phase 2 MTD was determined, when a dose limiting toxicity (DLT) occurred in 1 of 3 participants, the cohort was to be expanded to 6 participants. If a DLT occurred in 2 or more participants, accrual to the cohort was stopped, as the MTD was exceeded. A DLT was defined as an adverse event (AE) occurring in Cycle 1 (28 days) that was possibly related to study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0, ≥Grade 3 nonhematologic toxicity (except for nausea/vomiting without maximal symptomatic/prophylactic treatment) possibly or likely related to the study medication;CTCAE Grade 4 hematological toxicity of \>5 days duration; Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; CTCAE ≥Grade 2 thrombocytopenia plus bleeding; CTCAE ≥Grade 3 prolonged QTc interval.

Time frame: Baseline up to Day 28 (Cycle 1)

Secondary Outcomes

Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314

AUC0-∞ was calculated from the area under the concentration versus time curve from time 0 to infinity of LY2090314 when administered alone.

Time frame: Cycle 1 Day 1 of a 28 day cycle

PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)

AUC0-∞ was calculated from the area under the concentration versus time curves of LY2090314 from time zero to infinity when coadministered with Pem and Carb.

Time frame: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314

Time frame: Cycle 1 Day 1 of a 28-day cycle

PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)

Data from ClinicalTrials.gov

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