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A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LY2157299

Sorafenib

Placebo

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring transforming growth factor beta (TGF-β)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have histological evidence of a diagnosis of HCC not amenable to curative surgery.
Have Child-Pugh Class A.
Have the presence of measurable disease.
Have adequate organ function.
Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
If male or female 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.
If females with childbearing potential, must have had a negative serum pregnancy test 7 days prior to the first dose of study drug.
Are able to swallow capsules or tablets.
Have available diagnostic or biopsy tumor tissue.

Exclusion Criteria:

Have received previous systemic treatment for advanced disease.
Have known HCC with fibro-lamellar or mixed histology.
Have presence of clinically relevant ascites.
Have had a liver transplant.
Have moderate or severe cardiac disease.
Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.
Have experienced Grade 3 or 4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention.
Have esophageal or gastric varices that require immediate intervention or represent a high bleeding risk.
Had major surgery within 4 weeks prior to the study randomization.

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

150 milligram (mg) Galunisertib Monotherapy

150 mg Galunisertib + 400 mg Sorafenib Therapy

400 mg Sorafenib + Placebo Therapy

Arm Description

150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle).

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Outcomes

Primary Outcome Measures

Overall Survival (OS): Number of Events

OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported.

Secondary Outcome Measures

Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib

Population mean (between-subject coefficient variance [CV %]) apparent clearance.

Population Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib

Population Vss [distribution of galunisertib in the body at steady state] after a single dose of galunisertib.

Time to Tumor Progression (TTP)

TTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Progression-Free Survival (PFS)

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score

EORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much). Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.

Change From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score

The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem.

Full Information

NCT ID

NCT02178358

First Posted

June 12, 2014

Last Updated

February 14, 2022

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02178358

Brief Title

A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma

Official Title

A Randomized Phase 2 Study of LY2157299 Versus LY2157299 - Sorafenib Combination Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

August 8, 2014 (Actual)

Primary Completion Date

June 30, 2017 (Actual)

Study Completion Date

February 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2157299 in participants with hepatocellular carcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

transforming growth factor beta (TGF-β)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

132 (Actual)

8. Arms, Groups, and Interventions

Arm Title

150 milligram (mg) Galunisertib Monotherapy

Arm Type

Experimental

Arm Description

150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle).

Arm Title

150 mg Galunisertib + 400 mg Sorafenib Therapy

Arm Type

Experimental

Arm Description

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Arm Title

400 mg Sorafenib + Placebo Therapy

Arm Type

Placebo Comparator

Arm Description

Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Intervention Type

Drug

Intervention Name(s)

LY2157299

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally

Primary Outcome Measure Information:

Title

Overall Survival (OS): Number of Events

Description

Time Frame

Randomization to Date of Death from Any Cause (Up To 24 Months)

Secondary Outcome Measure Information:

Title

Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib

Description

Population mean (between-subject coefficient variance [CV %]) apparent clearance.

Time Frame

Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1

Title

Population Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib

Description

Population Vss [distribution of galunisertib in the body at steady state] after a single dose of galunisertib.

Time Frame

Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1

Title

Time to Tumor Progression (TTP)

Description

Time Frame

Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up To 24 Months)

Title

Progression-Free Survival (PFS)

Description

Time Frame

Randomization to Measured Progressive Disease or Death (Up To 24 Months)

Title

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Description

Time Frame

Randomization to Measured Progressive Disease (Up To 24 Months)

Title

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score

Description

Time Frame

Baseline, 24 Months

Title

Change From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score

Description

Time Frame

Baseline, 24 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have histological evidence of a diagnosis of HCC not amenable to curative surgery. Have Child-Pugh Class A. Have the presence of measurable disease. Have adequate organ function. Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. If male or female 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. If females with childbearing potential, must have had a negative serum pregnancy test 7 days prior to the first dose of study drug. Are able to swallow capsules or tablets. Have available diagnostic or biopsy tumor tissue. Exclusion Criteria: Have received previous systemic treatment for advanced disease. Have known HCC with fibro-lamellar or mixed histology. Have presence of clinically relevant ascites. Have had a liver transplant. Have moderate or severe cardiac disease. Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection. Have experienced Grade 3 or 4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention. Have esophageal or gastric varices that require immediate intervention or represent a high bleeding risk. Had major surgery within 4 weeks prior to the study randomization.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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

Beijing

ZIP/Postal Code

100036

Country

China

Facility Name

City

Bengbu

ZIP/Postal Code

233004

Country

China

Facility Name

City

Changchun

ZIP/Postal Code

130012

Country

China

Facility Name

City

Hangzhou

ZIP/Postal Code

310016

Country

China

Facility Name

City

Hefei

ZIP/Postal Code

230022

Country

China

Facility Name

City

Hong Kong

Country

Hong Kong

Facility Name

City

Kowloon

Country

Hong Kong

Facility Name

City

Incheon

ZIP/Postal Code

405-760

Country

Korea, Republic of

Facility Name

City

Seoul

ZIP/Postal Code

135 720

Country

Korea, Republic of

Facility Name

City

Gwei Shan Township

ZIP/Postal Code

333

Country

Taiwan

Facility Name

City

Liouying/Tainan

ZIP/Postal Code

736

Country

Taiwan

Facility Name

City

Puzih City

ZIP/Postal Code

613

Country

Taiwan

Facility Name

City

Tainan

ZIP/Postal Code

70403

Country

Taiwan

Facility Name

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

Facility Name

City

Taoyuan

ZIP/Postal Code

33378

Country

Taiwan

Facility Name

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and european union (EU), whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Learn more about this trial

A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma

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