A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

NCT01287520 | Completed Phase 1 Results

• 2 other identifiers: 11613I2H-MC-JWYA
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline up to Day 28 (Cycle 1)

Secondary Outcomes (10)

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

  Cycle 1 Day 1 of a 28 day cycle

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

  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

  Cycle 1 Day 1 of a 28-day cycle

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

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

• Number of Participants With Best Overall Tumor Response

  Baseline up to Cycle 9 (Cycle 1 was 28 days, Cycles 2 to 9 were 21 days)

Study Arms (1)

LY2090314/pemetrexed/carboplatin

EXPERIMENTAL

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.

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

Interventions

LY2090314 DRUG

Administered intravenously

LY2090314/pemetrexed/carboplatin

pemetrexed DRUG

Administered intravenously

Also known as: Alimta, LY231514

LY2090314/pemetrexed/carboplatin

Carboplatin DRUG

Administered intravenously

LY2090314/pemetrexed/carboplatin

ranitidine OTHER

Per I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine given as pretreatment to LY2090314 for stomach pain.

LY2090314/pemetrexed/carboplatin

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (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

Location

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

Location

Related Publications (1)

• 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.

  PMID: 26403509 DERIVED

MeSH Terms

Interventions

3-(9-fluoro-2-(piperidin-1-ylcarbonyl)-1,2,3,4-tetrahydro(1,4)diazepino(6,7,1-hi)indol-7-yl)-4-imidazo(1,2-a)pyridin-3-yl-1H-pyrrole-2,5-dione; Pemetrexed; Carboplatin; Ranitidine

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Furans; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2011
• First Posted: February 1, 2011
• Study Start: November 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: February 25, 2019
• Results First Posted: February 25, 2019

Record last verified: 2018-10

Locations

US (2)