Clinical trial NCT01393990: A Study of LY2228820 in Participants With Advanced Cancer
Official title: A Phase 1 Study of an Oral p38 MAPK Inhibitor in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-07-14
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine a safe dose of LY2228820 that may be given to participants with advanced cancer. Part A of this study will consist of dose escalation, and Part B will consist of dose confirmation.


Eligibility criteria: Inclusion Criteria:

* Have histological or cytological evidence of a diagnosis of cancer (including lymphoma) that is advanced or metastatic disease for which no therapy of higher priority (approved therapies or therapies with published substantial evidence of effectiveness) is available, or for whom no standard therapy exists
* Have the presence of measurable or nonmeasurable disease as defined by Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
* Have adequate hematologic, renal, and hepatic organ function
* Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
* Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or other investigational therapy for at least 14 days (42 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy
* Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
* Females with child bearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug
* Have an estimated life expectancy of ≥ 12 weeks
* Are able to swallow capsules and/or tablets

Exclusion Criteria:

* Have received treatment within 14 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
* Have a history of major surgical resection involving the stomach or small bowel, or have serious preexisting medical conditions (based on judgment of the investigator)
* Have symptomatic central nervous system malignancy or metastasis (screening is not required)
* Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
* Have an active hematologic malignancy other than lymphoma
* Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Screening at baseline will not be required for enrollment
* Concurrent administration of any immunosuppressive therapy
* Females who are pregnant or lactating
* Have received, within 7 days of the initial dose of study drug, either grapefruit juice or treatment with a drug that is a known inhibitor or inducer of Cytochrome P450 Enzyme 3A4 (CYP3A4). In addition, participants should not receive grapefruit juice or treatment with a CYP3A4 inhibitor or inducer during the study

Primary outcomes:
measure: Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)
timeFrame: Baseline to study completion (Up to 41 months)
Secondary outcomes:
measure: Recommended Dose for Phase 2 Studies
timeFrame: Baseline to study completion (Up to 41 months)
measure: Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)]
timeFrame: Baseline to study completion (Up to 41 months)
measure: PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820
timeFrame: Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose
measure: PK: Maximum Plasma Concentration (Cmax) of LY2228820
timeFrame: Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose
measure: Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1
timeFrame: Cycle 1 Day 1: predose, 1, 2, 4, and 6 h postdose
Other outcomes:
Locations:
city: Rochester
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: Minnesota
city: San Antonio
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: Texas
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: