A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Advanced Cancer

Treatments: Drug: Carboplatin; Drug: LY2090314; Other: ranitidine; Drug: pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT01287520

11613

I2H-MC-JWYA (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 25+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 1 patient group

LY2090314/pemetrexed/carboplatin

Experimental group

Description:

Part A, Cycle 1 (28 days): Intravenous doses of LY2090314 starting at 10 milligram (mg) were given on Day 1 followed by 10 mg LY2090314, 500 milligram per square meter (mg/m\^2) pemetrexed (intravenous dose), and 5 or 6 area under the concentration-time curve (AUC) intravenous dose of carboplatin on Day 8. Part A, Cycle 2 (21 days): Pemetrexed and carboplatin given on Day 1 at the same dose administered in Cycle 1. Part A, Cycle 3 (21 days) and beyond: LY2090314, Pemetrexed and carboplatin were given on Day 1 at the same dose administered in Cycle 1. LY2090314 doses were escalated until the maximum tolerated dose (MTD) was reached. Part B: Dose determined in Part A was administered. Participants were allowed to continue the combination treatment if they were receiving therapeutic benefit until they fulfilled one of the criteria for discontinuation.

Treatment:

Drug: LY2090314

Other: ranitidine

Drug: pemetrexed

Drug: Carboplatin