A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Cancer	Drug: LY2090314; Drug: pemetrexed; Drug: Carboplatin	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	41 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin
Study Start Date :	November 2007
Actual Primary Completion Date :	April 2011
Actual Study Completion Date :	April 2011

Arms and Interventions

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Arm

Intervention/treatment

Experimental: LY2090314/pemetrexed/carboplatin; In Part A, intravenous (IV) doses of LY2090314 starting at 10 mg will be given on day 1 of cycle 1 (28 days) followed by 10 mg dose of LY2090314, 500 mg/m^2 IV dose of pemetrexed, and 5 or 6 AUC IV dose of carboplatin on day 8 of cycle 1. In Cycle 2, pemetrexed and carboplatin will be given on day 1 at same dose administered in cycle 1. In Cycle 3 and beyond, LY2090314, pemetrexed and carboplatin will be given on day 1 in the same dose administered in cycle 1. Cycles 2 and beyond are 21 days in length. Doses of LY2090314 will be escalated until the maximum tolerated dose is reached. In Part B, dose determined by Part A will be administered. Patients may continue the combination treatment if they are receiving therapeutic benefit until they fulfill one of the criteria for discontinuation.

Drug: LY2090314; Administered intravenously Drug: pemetrexed; Administered intravenously; Other Names: Alimta; LY231514 Drug: Carboplatin; Administered intravenously

Outcome Measures

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Primary Outcome Measures :

1. Recommended dose for Phase 2 studies [ Time Frame: Baseline to study completion ]

Secondary Outcome Measures :

1. Pharmacokinetics, area under the concentration-time curve (AUC) [ Time Frame: Days 1, 2, 8, and 9 of Cycle 1, and Days 1 and 2 of Cycle 2, and Day 1 for Cycles 3 and beyond. ]
2. Pharmacokinetics, maximum plasma concentration (Cmax) [ Time Frame: Days 1, 2, 8, and 9 of Cycle 1, and Days 1 and 2 of Cycle 2, and Day 1 for Cycles 3 and beyond. ]

Eligibility Criteria

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Ages Eligible for Study:	25 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 three 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.
• 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 the discretion of the investigator).
• Have one of the following conduction abnormalities: QTc prolongation >450 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/equal to 140 mm Hg, and diastolic blood pressure greater than/equal to 90 mm Hg that is not controlled by medical therapy.
• Have a 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. Patients with a history of arrhythmia which is symptomatic or requires treatment.
• Have chronic atrial fibrillation and/or bradycardia.
• Have uncorrected electrolyte disorders including potassium <3.4 mEq/L (<3.4 mmol/l), calcium <8.4 mg/dL (2.1 mmol/L), or magnesium <1.2 mg/dL (<0.62 mmol/L).
• Have symptomatic central nervous system malignancy or metastasis (screening not required).
• Have a hematologic malignancy.
• Females who are pregnant or lactating.

Contacts and Locations

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Locations

United States, Florida
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
United States, Tennessee
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.
Nashville, Tennessee, United States

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director:	Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gray JE, Infante JR, Brail LH, Simon GR, Cooksey JF, Jones SF, Farrington DL, Yeo A, Jackson KA, Chow KH, Zamek-Gliszczynski MJ, Burris HA 3rd. A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin. Invest New Drugs. 2015 Dec;33(6):1187-96. doi: 10.1007/s10637-015-0278-7. Epub 2015 Sep 25.

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT01287520 History of Changes
Other Study ID Numbers:	11613; I2H-MC-JWYA ( Other Identifier: Eli Lilly and Company )
First Posted:	February 1, 2011
Last Update Posted:	June 21, 2011
Last Verified:	June 2011

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Carboplatin; Pemetrexed	Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors