A Study of LY2228820 in Participants With Advanced Cancer

NCT01393990 | Completed Phase 1 Results

• 2 other identifiers: 12284I1D-MC-JIAD
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)

  Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after the administration of at least 1 dose of study drug, regardless of causality. A summary of serious AEs (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

  Baseline to study completion (Up to 41 months)

Secondary Outcomes (5)

• Recommended Dose for Phase 2 Studies

  Baseline to study completion (Up to 41 months)

• Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)]

  Baseline to study completion (Up to 41 months)

• PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820

  Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose

• PK: Maximum Plasma Concentration (Cmax) of LY2228820

  Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose

• Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1

  Cycle 1 Day 1: predose, 1, 2, 4, and 6 h postdose

Study Arms (1)

LY2228820

EXPERIMENTAL

The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D). Part A: Participants received escalating doses of 10, 20, 40, 65, 90, 120, 160, 200, 300, 420 and 560 milligrams (mg) of LY2228820 every 12 hours on Days 1 through 14 of a 28-day cycle. Part B: Participants received 420 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Participants received midazolam orally 2 days before the first dose and again after the morning dose of study drug on Day 8 during the first cycle of treatment. Part C: Participants received 300 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Part D: Participants received 200 mg and 300 mg of LY2228820 in combination with tamoxifen.

Drug: LY2228820; Drug: Midazolam; Drug: Tamoxifen

Interventions

LY2228820 DRUG

Administered orally

Also known as: p38 MAP kinase

LY2228820

Midazolam DRUG

LY2228820

Tamoxifen DRUG

LY2228820

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

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.

Rochester, Minnesota, 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.

San Antonio, Texas, United States

Location

MeSH Terms

Interventions

ralimetinib; p38 Mitogen-Activated Protein Kinases; Midazolam; Tamoxifen

Intervention Hierarchy (Ancestors)

Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

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: July 12, 2011
• First Posted: July 14, 2011
• Study Start: September 4, 2008
• Primary Completion: February 1, 2013
• Study Completion: December 14, 2013
• Last Updated: March 24, 2020
• Results First Posted: March 24, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)