A Study of LY2157299 in Participants With Unresectable Hepatocellular Cancer (HCC)

A Phase 1b Study of LY2157299 in Combination With Sorafenib in Patients With Unresectable Hepatocellular Carcinoma

The main purpose of this study is to evaluate safety and tolerability of LY2157299 when combined with sorafenib in Japanese hepatocellular carcinoma (HCC) participants.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: LY2157299; Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 277 8577
    • 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.
  • Kanagawa, Japan, 241-8515
    • 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.
  • Suita-shi, Japan, 565-0871
    • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have histological evidence of a diagnosis of HCC (except HCC with fibrolamellar or mixed histology) not amenable to curative surgery.
• Have Child-Pugh Class A.
• Have the presence of measurable or evaluable lesion as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A measurable or evaluable lesion showing demonstrable progression after locoregional therapy could be also included.
• Have not received sorafenib prior to enrollment.
• Have resolution to Grade less than or equal 1 by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 of all clinically significant toxic effects of prior locoregional therapy, surgery, chemoembolization, systemic chemotherapy.
• Have a performance status of less than or equal 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

Exclusion Criteria:

• Are currently enrolled, or discontinued within 28 days prior to enrollment from, a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have undergone major surgery within 28 days prior to enrollment.
• Have undergone hepatic locoregional therapy (including radiation, surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, cryoablation, percutaneous ethanol injection, or percutaneous microwave coagulation therapy) within 28 days prior to enrollment.

• Have moderate or severe cardiac disease.

  • Myocardial infarction within 6 months prior to enrollment, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension.
  • Documented major electrocardiogram (ECG) abnormalities at the investigator's discretion within 28 days prior to enrollment.
  • Major abnormalities documented by echocardiography with Doppler at investigator's direction within 28 days prior to enrollment.
  • Have persistently elevated brain natriuretic peptide (BNP) or elevated troponin I within 14 days prior to enrollment.
  • Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress.
  • Have a history of cardiac or aortic surgery.
• Have undergone liver transplant.
• Are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2157299 + Sorafenib; LY2157299 will be administered orally twice daily for 14 days, followed by 14 days with no study drug per 28-day cycle. Sorafenib will be administered orally twice daily for 28 days, in each cycle.	Drug: LY2157299; LY2157299 administered orally; Drug: Sorafenib; Sorafenib administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with LY2157299 Dose-Limiting Toxicities (DLT)	Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve (AUC) of LY2157299	Cycle 1 Day1: predose through 6 hours post dose; Cycle1 Day14: predose through 24 hours post dose
PK: Maximum Observed Plasma Concentration (Cmax) of LY2157299	Cycle 1 Day 1: Predose through 6 hours post dose; Cycle 1 Day 14: Predose through 24 hours post dose
Time to Progression (TTP)	Baseline to objective progressive disease (estimated as 6 months)
Progression-free Survival (PFS)	Baseline to objective progressive disease or death (estimated as 6 months)
The Number of Participants with Best Response of Partial Response (PR), Complete Response (CR), Stable Disease (SD), or Progressive Disease (PD)	Baseline to objective progressive disease (estimated as 6 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2014
• Primary Completion (Actual): July 19, 2017
• Study Completion (Actual): December 25, 2019

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (Estimate): September 15, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 14856; H9H-JE-JBAP (Other Identifier: Eli Lilly and Company)