Clinical trial NCT01648764: A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread
Official title: Phase 1 Dose Escalation Study of LY2334737 Using 2 Dosing Regimens in Patients With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Solid Tumor
Solid Tumor
Metastatic Tumor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-07-24
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate two different dosing regimens of LY2334737 in participants with cancer that is advanced and/or has spread to other parts of the body. Information about side effects will be collected.

Detailed description: This study will consist of a Dose Escalation Phase (Arms A and B) followed by a Dose Confirmation Phase.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of advanced and/or metastatic cancer (including lymphoma) for which no treatment of higher priority exists
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Estimated life expectancy of more than 12 weeks
* Have discontinued all previous therapies for cancer for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) and recovered from acute effects of therapy
* Have discontinued radiotherapy more than one week before enrolling in the study and have recovered from the acute effects of therapy
* Have adequate organ function
* Follow your doctor's directions and live close enough to the study site so you can continue to go to the clinic for follow-up
* Are willing and able to swallow capsules and follow study procedures
* Have given written informed consent prior to any study-specific procedures
* Males and females with reproductive potential should use medically approved contraceptive precautions during the study and for 6 months following the last dose of study drug
* Females with child-bearing potential must have had a negative urine or serum pregnancy test 7 days prior to the first dose of study drug

Exclusion Criteria:

* Have gastrointestinal diseases or prior surgery that may interfere with the absorption of medication taken by mouth
* Females who are pregnant or lactating
* Symptomatic central nervous system malignancy or metastasis
* Known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
* Liver cirrhosis or chronic hepatitis
* Acute or chronic leukemia
* Are currently receiving treatment with valproic acid (VPA) and its derivatives, or if you have a history of intolerance to VPA
* Known hypersensitivity to gemcitabine

Primary outcomes:
measure: Recommended Dose for Phase 2 Studies
timeFrame: Baseline up to 28 days postdose in Cycle 1 (28-day cycle)
Secondary outcomes:
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for LY2334737
timeFrame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for 2'2'-Difluorodeoxycytidine (dFdC)
timeFrame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours post dose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours post dose of 28-day cycle
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for Difluorodeoxyuridine (dFdU)
timeFrame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
measure: Pharmacokinetics: Maximum Plasma Concentration (Cmax)
timeFrame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
measure: Number of Participants With Best Overall Response (BOR)
timeFrame: Baseline to measured disease progression up to 33 weeks
measure: Progression-Free Survival (PFS)
timeFrame: Baseline to measured disease progression or death up to 33 weeks
measure: Percentage of Participants With Changes in QT Interval (>30 Milliseconds) From Baseline
timeFrame: Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21, 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose (28-day cycles)
measure: Percentage of Participants With Changes in R-R Interval From Baseline
timeFrame: Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21: 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose
measure: Pharmacokinetics: Minimum Plasma Concentration (Cmin)
timeFrame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7, 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Other outcomes:
measure: Number of Participants With Dose-Limiting Toxicity (DLT)
timeFrame: Cycle 1 (28-day cycle)
Locations:
city: Philadelphia
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: Pennsylvania
city: Clichy
country: France
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.
city: Berlin
country: Germany
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.
city: Nürnberg
country: Germany
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.
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: