Clinical trial NCT01287520: A Study of LY2090314 in Patients With Advanced or Metastatic Cancer
Official title: Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-02-01
Enrollment: 41
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 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

Primary outcomes:
measure: Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD])
timeFrame: Baseline up to Day 28 (Cycle 1)
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314
timeFrame: Cycle 1 Day 1 of a 28 day cycle
measure: PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)
timeFrame: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle
measure: PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314
timeFrame: Cycle 1 Day 1 of a 28-day cycle
measure: PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)
timeFrame: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle
measure: Number of Participants With Best Overall Tumor Response
timeFrame: Baseline up to Cycle 9 (Cycle 1 was 28 days, Cycles 2 to 9 were 21 days)
measure: Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Pemetrexed (Pem)
timeFrame: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle
measure: PK Parameter: Maximum Plasma Concentration (Cmax) of Pemetrexed (Pem)
timeFrame: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle
measure: PK Parameter: AUC0-∞ of Free Carboplatin (Carb)
timeFrame: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle
measure: PK Parameter: Cmax of Free Carboplatin
timeFrame: Cycle 1, Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle
measure: Pharmacodynamic (PD) Changes in Beta-Catenin (β-catenin)
timeFrame: Baseline, Cycle 1 , Day 1 of a 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycles
Other outcomes:
Locations:
city: Tampa
country: United States
facility: 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.
state: Florida
city: Nashville
country: United States
facility: 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.
state: Tennessee
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.