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A Study of LY2157299 in Participants With Hepatocellular Carcinoma

Primary Purpose

Carcinoma, Hepatocellular

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LY2157299

Sorafenib

Ramucirumab

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

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
Part A: Serum alpha fetoprotein greater than or equal to 1.5 Upper Limits of Normal, Part B: Serum alpha fetoprotein less than 1.5 Upper Limits of Normal. Not applicable for Part C or D
Child-Pugh Stage: A or B7 for Parts A & B, A for Part C, and D
Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). A lesion that has been previously treated by local therapy will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy
Have given written informed consent prior to any study-specific procedures
Have adequate hematologic, hepatic and renal function
Have a performance status of equal to or less than 1 on the Eastern Cooperative Oncology Group (ECOG) scale
For Parts A & B: Have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment. For Part C: not received previous systemic treatment. For Part D: have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment or have not received prior systemic treatment.
For Parts A, B, and D: have discontinued sorafenib for at least 2 weeks
Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
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 childbearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug
Are able to swallow capsules or tablets

Exclusion Criteria:

Are currently enrolled in, or discontinued within the last 28 days from a clinical trial involving an investigational drug or device or not approved use of a drug or device (other than the study drug 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
Known HCC with fibro-lamellar or mixed histology
Presence of clinically relevant ascites
History of liver transplant requiring increased immunosuppressive therapy. (Participants on maintenance immunosuppressive therapy after liver transplant are eligible for Part A & B)
Have received more than 1 line of systemic treatment in Parts A, B and D
Have moderate or severe cardiac disease:
1. Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension
2. Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion
3. Have major abnormalities documented by echocardiography with Doppler
4. Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress
Have serious preexisting medical conditions that, in the opinion of the investigator, that cannot be adequately controlled with appropriate therapy or would preclude participation in this study
Females who are pregnant or lactating
Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for that disease for a minimum of 3 years. At the discretion of the investigator, hormone-refractory prostate cancer participants who are stable on GnRH agonist therapy and breast cancer participants who are stable on antiestrogen therapy may have that treatment continued
Have active infection that would interfere with the study objectives or influence study compliance
For Part C, have a known hypersensitivity to sorafenib or its excipients
For Part D, have a serious illness or medical condition(s), including but not limited to the following:
1. The participant has undergone major surgery within 28 days prior to randomization or has undergone central venous access device placement within 7 days prior to randomization
2. The participant has uncontrolled arterial hypertension ≥150 / ≥90 millimeters of mercury (mm Hg) despite standard medical management

Sites / Locations

Highlands Oncology Group
University of California, San Francisco
Georgetown University Medical Center
MD Anderson Cancer Center Orlando
Northwestern University
Indiana Univ Melvin & Bren Simon Cancer Center
Lahey Clinic Medical Center
Weill Cornell Medical College
Memorial Sloan Kettering Cancer Center
Thomas Jefferson University
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.
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 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Part A Cohort 1-160 milligram (mg) LY2157299

Part A Cohort 2 - 300 mg LY2157299

Part B - 300 mg LY2157299

Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib

Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib

Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab

Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab

Arm Description

Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm. As of May 25,2012, all newly enrolled participants will receive 300 mg LY2157299. 80 mg LY2157299 given orally twice daily (BID) for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Outcomes

Primary Outcome Measures

Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)

Biomarker response was defined as a > 20% decrease in the biomarker AFP from baseline during 8 weeks of treatment. Data presented is median overall survival of those participants who achieved the defined biomarker response. Participants enrolled in Part A had a baseline AFP level of >1.5 upper limit normal (ULN). Participants enrolled in Part B had baseline AFP level <1.5 ULN.

Change From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-β) to Overall Survival (OS)

Biomarker response was defined as a > 20% decrease in the biomarker TGF-B from baseline. Data presented is median overall survival of those participants who achieved biomarker response.

Time to Progression (TTP)

TTP is measured from the date of first dose to the first date of progression of disease based on the investigator review of tumor response using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Secondary Outcome Measures

Population Pharmacokinetics (PK) Mean Population Clearance of Galunisertib

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

Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials

Overall Survival (OS)

OS duration is measured from the date of first dose to the date of death from any cause.

Progression Free Survival (PFS)

PFS duration is measure from the date of first dose to the first date of objective progression of disease or death from any cause. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Percentage of Participants Achieving an Objective Response (Response Rate)

The percentage of participants who achieved best overall response of either Complete Response (CR) or Partial Response (PR). The overall response rate for each dose with be estimated by dividing the number of confirmed responders by the number of participants who received at least one dose of study drug. Per RECIST v.1.0 criteria CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.

Duration of Tumor Response (DoR)

DoR is measured from the date of the first objective status assessment of a Complete Response (CR) or Partial Response (PR), as determined by RECIST v1.1, to the first date of objective progression of disease or death from any cause. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Time to Treatment Failure (TTF)

TTF is measured from the date of first dose until the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause.

Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72; FACT-Hep score range 1-180, and Trial-Outcome Index (TOI) score range 1-128, to assess health related quality of life in participants with cancer. Higher scores reflect a better health state.

Time to Worsening (TTW) of Symptoms (FACT-Hep)

Time to worsening of symptoms used minimally important differences to evaluate Physical Well Being (PWB), Functional Well Being (FWB), Hepatocellular Cancer Symptoms (HCS), National Comprehensive Cancer Network (NCCN)/FACT Hepatocellular Symptoms (FHS), Trial-Outcome Index (TOI). PWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; FWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; HCS time to worsening was defined as participants who had change in a subscale of ≥ 5 point decrease from baseline; FHS time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; TOI time to Worsening was defined as participants who had change in the subscale of ≥ 7 point decrease from baseline.

Full Information

NCT ID

NCT01246986

First Posted

November 1, 2010

Last Updated

December 21, 2020

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01246986

Brief Title

A Study of LY2157299 in Participants With Hepatocellular Carcinoma

Official Title

Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

March 30, 2011 (Actual)

Primary Completion Date

June 6, 2019 (Actual)

Study Completion Date

December 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to estimate the median time to progression in participants with hepatocellular carcinoma (HCC) when treated with LY2157299 as monotherapy and in combination with sorafenib or ramucirumab.

Detailed Description

The study consists of four Parts: Part A where HCC participants with an increased alpha-fetoprotein (AFP) level will be treated with either 160 milligrams (mg) LY2157299 or 300 mg LY2157299. Part B where HCC participants with a normal AFP level will be treated with 300 mg LY2157299, Part C where treatment-naïve HCC participants will be treated with 160 mg LY2157299 + sorafenib or 300 mg LY2157299 + sorafenib, and Part D where HCC participants will be treated with either 160 mg or 300 mg LY2157299 + ramucirumab. Participants who continue to receive benefit from treatment at the time that the study is considered completed, may enter the treatment extension period and continue to receive the study treatment. The end of the study is the date of last visit or last scheduled procedure for the last active subject in the study.

6. Conditions and Keywords

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

Carcinoma, Hepatocellular

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

204 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A Cohort 1-160 milligram (mg) LY2157299

Arm Type

Experimental

Arm Description

Arm Title

Part A Cohort 2 - 300 mg LY2157299

Arm Type

Experimental

Arm Description

Arm Title

Part B - 300 mg LY2157299

Arm Type

Experimental

Arm Description

Arm Title

Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib

Arm Type

Experimental

Arm Description

Arm Title

Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib

Arm Type

Experimental

Arm Description

Arm Title

Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab

Arm Type

Experimental

Arm Description

Arm Title

Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab

Arm Type

Experimental

Arm Description

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)

Ramucirumab

Other Intervention Name(s)

LY30098016

Intervention Description

Administered IV

Primary Outcome Measure Information:

Title

Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)

Description

Time Frame

Baseline, discontinuation from any cause (Up to 83 months)

Title

Change From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-β) to Overall Survival (OS)

Description

Biomarker response was defined as a > 20% decrease in the biomarker TGF-B from baseline. Data presented is median overall survival of those participants who achieved biomarker response.

Time Frame

Baseline,discontinuation from any cause (Up to 83 months)

Title

Time to Progression (TTP)

Description

Time Frame

Randomization to date of first measured progressive disease (Up to 36 Weeks)

Secondary Outcome Measure Information:

Title

Population Pharmacokinetics (PK) 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

Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials

Time Frame

Cycle 1 (28 Days)

Title

Overall Survival (OS)

Description

OS duration is measured from the date of first dose to the date of death from any cause.

Time Frame

Randomization to date of death from any cause (Up to 83 months)

Title

Progression Free Survival (PFS)

Description

Time Frame

Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)

Title

Percentage of Participants Achieving an Objective Response (Response Rate)

Description

Time Frame

Randomization to measured progressive disease (Up to 36 Weeks)

Title

Duration of Tumor Response (DoR)

Description

Time Frame

Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)

Title

Time to Treatment Failure (TTF)

Description

TTF is measured from the date of first dose until the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause.

Time Frame

Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause (Up to 75 Weeks)

Title

Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score

Description

Time Frame

Baseline, Day 1 Cycle 4

Title

Time to Worsening (TTW) of Symptoms (FACT-Hep)

Description

Time Frame

Baseline to the worsening of symptoms (up to 567 days)

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 Part A: Serum alpha fetoprotein greater than or equal to 1.5 Upper Limits of Normal, Part B: Serum alpha fetoprotein less than 1.5 Upper Limits of Normal. Not applicable for Part C or D Child-Pugh Stage: A or B7 for Parts A & B, A for Part C, and D Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). A lesion that has been previously treated by local therapy will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy Have given written informed consent prior to any study-specific procedures Have adequate hematologic, hepatic and renal function Have a performance status of equal to or less than 1 on the Eastern Cooperative Oncology Group (ECOG) scale For Parts A & B: Have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment. For Part C: not received previous systemic treatment. For Part D: have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment or have not received prior systemic treatment. For Parts A, B, and D: have discontinued sorafenib for at least 2 weeks Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures 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 childbearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug Are able to swallow capsules or tablets Exclusion Criteria: Are currently enrolled in, or discontinued within the last 28 days from a clinical trial involving an investigational drug or device or not approved use of a drug or device (other than the study drug 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 Known HCC with fibro-lamellar or mixed histology Presence of clinically relevant ascites History of liver transplant requiring increased immunosuppressive therapy. (Participants on maintenance immunosuppressive therapy after liver transplant are eligible for Part A & B) Have received more than 1 line of systemic treatment in Parts A, B and D Have moderate or severe cardiac disease: Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension Have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion Have major abnormalities documented by echocardiography with Doppler Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress Have serious preexisting medical conditions that, in the opinion of the investigator, that cannot be adequately controlled with appropriate therapy or would preclude participation in this study Females who are pregnant or lactating Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for that disease for a minimum of 3 years. At the discretion of the investigator, hormone-refractory prostate cancer participants who are stable on GnRH agonist therapy and breast cancer participants who are stable on antiestrogen therapy may have that treatment continued Have active infection that would interfere with the study objectives or influence study compliance For Part C, have a known hypersensitivity to sorafenib or its excipients For Part D, have a serious illness or medical condition(s), including but not limited to the following: The participant has undergone major surgery within 28 days prior to randomization or has undergone central venous access device placement within 7 days prior to randomization The participant has uncontrolled arterial hypertension ≥150 / ≥90 millimeters of mercury (mm Hg) despite standard medical management

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 - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

Highlands Oncology Group

City

Fayetteville

State/Province

Arkansas

ZIP/Postal Code

72703

Country

United States

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94158

Country

United States

Facility Name

Georgetown University Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

MD Anderson Cancer Center Orlando

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Indiana Univ Melvin & Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Lahey Clinic Medical Center

City

Burlington

State/Province

Massachusetts

ZIP/Postal Code

01805

Country

United States

Facility Name

Weill Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

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

Nedlands

State/Province

Western Australia

ZIP/Postal Code

6009

Country

Australia

Facility Name

City

Greenslopes

ZIP/Postal Code

4120

Country

Australia

Facility Name

City

Heidelberg

ZIP/Postal Code

3084

Country

Australia

Facility Name

City

St. Leonards

ZIP/Postal Code

2065

Country

Australia

Facility Name

City

Brest

ZIP/Postal Code

29609

Country

France

Facility Name

City

Caen

ZIP/Postal Code

14033

Country

France

Facility Name

City

Clichy

ZIP/Postal Code

92110

Country

France

Facility Name

City

Creteil

ZIP/Postal Code

94010

Country

France

Facility Name

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

City

Lyon

ZIP/Postal Code

69317

Country

France

Facility Name

City

Marseille

ZIP/Postal Code

13273

Country

France

Facility Name

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

City

Paris

ZIP/Postal Code

75012

Country

France

Facility Name

City

Pessac

ZIP/Postal Code

33604

Country

France

Facility Name

City

Saint Etienne

ZIP/Postal Code

42055

Country

France

Facility Name

City

Saint Herblain

ZIP/Postal Code

44805

Country

France

Facility Name

City

Strasbourg

ZIP/Postal Code

67085

Country

France

Facility Name

City

Vandoeuvre Les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

City

Göttingen

ZIP/Postal Code

37075

Country

Germany

Facility Name

City

Köln

ZIP/Postal Code

50937

Country

Germany

Facility Name

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

City

Bari

ZIP/Postal Code

70124

Country

Italy

Facility Name

City

Rome

ZIP/Postal Code

00168

Country

Italy

Facility Name

City

Rozzano

ZIP/Postal Code

20089

Country

Italy

Facility Name

City

Auckland

ZIP/Postal Code

1023

Country

New Zealand

Facility Name

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

City

Madrid

ZIP/Postal Code

28007

Country

Spain

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 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/

Citations:

PubMed Identifier

32210440

Citation

Giannelli G, Santoro A, Kelley RK, Gane E, Paradis V, Cleverly A, Smith C, Estrem ST, Man M, Wang S, Lahn MM, Raymond E, Benhadji KA, Faivre S. Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-betaRI inhibitor galunisertib. PLoS One. 2020 Mar 25;15(3):e0222259. doi: 10.1371/journal.pone.0222259. eCollection 2020. Erratum In: PLoS One. 2020 Jun 25;15(6):e0235580. PLoS One. 2021 Jun 17;16(6):e0253671.

Results Reference

derived

PubMed Identifier

31995602

Citation

Addepalli A, Kalyani S, Singh M, Bandyopadhyay D, Mohan KN. CalPen (Calculator of Penetrance), a web-based tool to estimate penetrance in complex genetic disorders. PLoS One. 2020 Jan 29;15(1):e0228156. doi: 10.1371/journal.pone.0228156. eCollection 2020. Erratum In: PLoS One. 2020 Jun 25;15(6):e0235547.

Results Reference

derived

PubMed Identifier

30963691

Citation

Faivre S, Santoro A, Kelley RK, Gane E, Costentin CE, Gueorguieva I, Smith C, Cleverly A, Lahn MM, Raymond E, Benhadji KA, Giannelli G. Novel transforming growth factor beta receptor I kinase inhibitor galunisertib (LY2157299) in advanced hepatocellular carcinoma. Liver Int. 2019 Aug;39(8):1468-1477. doi: 10.1111/liv.14113. Epub 2019 Jun 3.

Results Reference

derived

PubMed Identifier

26632545

Citation

Li S, Yang F, Ren X. Immunotherapy for hepatocellular carcinoma. Drug Discov Ther. 2015 Oct;9(5):363-71. doi: 10.5582/ddt.2015.01054.

Results Reference

derived

Links:

URL

https://www.lillytrialguide.com/en-US/studies/liver-cancer/JBAK#?postal=

Description

A Study of LY2157299 in Participants With Hepatocellular Carcinoma

Learn more about this trial

A Study of LY2157299 in Participants With Hepatocellular Carcinoma

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