Carcinoma, HepatocellularPhase 2NCT01246986

A Study of LY2157299 in Participants With Hepatocellular Carcinoma

A Phase 2 study testing LY2157299, Sorafenib and Ramucirumab in people with Carcinoma, Hepatocellular, run by Eli Lilly and Company at 40 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Carcinoma, Hepatocellular
What is being tested?: LY2157299, Sorafenib and Ramucirumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 204 participants
Where: 40 sitesin 7 countries
Study dates: 30 Mar 2011to 24 Dec 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 13Show fewer

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

Who cannot join

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:

Show all 18Show fewer

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

Trial locations and contacts

40 sites in 7 countries.

Country

City, postcode or hospital

40 sites in 7 countries

France14 sites

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.
Brest, 29609
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.
Caen, 14033
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.
Clichy, 92110
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.
Créteil, 94010
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.
Lille, 59037
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.
Lyon, 69317
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.
Marseille, 13273
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.
Montpellier, 34295
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.
Paris, 75012
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.
Pessac, 33604
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
Saint-Etienne, 42055
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.
Saint-Herblain, 44805
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.
Strasbourg, 67085
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.
Vandœuvre-lès-Nancy, 54511

Other trials in France

United States10 sites

Lahey Clinic Medical Center
Burlington, Massachusetts, 01805
Northwestern University
Chicago, Illinois, 60611
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Indiana Univ Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Weill Cornell Medical College
New York, New York, 10021
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
MD Anderson Cancer Center Orlando
Orlando, Florida, 32806
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of California, San Francisco
San Francisco, California, 94158
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007

Other trials in United States

Germany6 sites

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.
Berlin, 13353
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.
Cologne, 50937
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.
Erlangen, 91054
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.
Göttingen, 37075
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.
Mainz, 55131
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.
Münster, 48149

Other trials in Germany

Australia4 sites

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.
Greenslopes, 4120
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
Heidelberg, 3084
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.
Nedlands, Western Australia, 6009
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.
St Leonards, 2065

Other trials in Australia

Italy3 sites

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.
Bari, 70124
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.
Rome, 00168
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.
Rozzano, 20089

Other trials in Italy

Spain2 sites

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.
Barcelona, 08035
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.
Madrid, 28007

Other trials in Spain

New Zealand1 site

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.
Auckland, 1023

Other trials in New Zealand

About this study

Official title: Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma

Read the 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.

Conditions: Carcinoma, Hepatocellular
Being tested: LY2157299, Sorafenib, Ramucirumab
Medical subject headings: Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LY2157299Drug
Administered orally
SorafenibDrug
Administered orally
RamucirumabDrug
Also called LY30098016
Administered IV

Study groups in NCT01246986
Study group	Role	What they receive
Part A Cohort 1-160 milligram (mg) LY2157299	Experimental	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. Receives: Drug: LY2157299
Part A Cohort 2 - 300 mg LY2157299	Experimental	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. Receives: Drug: LY2157299; Drug: Sorafenib
Part B - 300 mg LY2157299	Experimental	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. Receives: Drug: LY2157299
Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib	Experimental	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. Receives: Drug: LY2157299; Drug: Sorafenib
Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib	Experimental	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. Receives: Drug: LY2157299; Drug: Sorafenib
Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab	Experimental	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. Receives: Drug: LY2157299; Drug: Ramucirumab
Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab	Experimental	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. Receives: Drug: LY2157299; Drug: Ramucirumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, discontinuation from any cause (Up to 83 months)
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.
Measured: Baseline,discontinuation from any cause (Up to 83 months)
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.
Measured: Randomization to date of first measured progressive disease (Up to 36 Weeks)

Secondary outcomes (9)

Population Pharmacokinetics (PK) Mean Population Clearance of Galunisertib
Population mean (between-subject coefficient variance [CV %]) apparent clearance.
Measured: 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
Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials
Measured: Cycle 1 (28 Days)
Overall Survival (OS)
OS duration is measured from the date of first dose to the date of death from any cause.
Measured: Randomization to date of death from any cause (Up to 83 months)
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.
Measured: Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)
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.
Measured: Randomization to measured progressive disease (Up to 36 Weeks)
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.
Measured: Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)
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.
Measured: 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)
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.
Measured: Baseline, Day 1 Cycle 4
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.
Measured: Baseline to the worsening of symptoms (up to 567 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Mar 201124 Dec 2019

First posted24 Nov 2010 (estimated)
Study start30 Mar 2011
Primary completion6 Jun 2019
Study completion24 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 204 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01246986
Sponsor's protocol ID: 13665
Other IDs: H9H-MC-JBAK, 2010-022338-10
Status last verified: Jan 2020
First submitted: 1 Nov 2010
Last updated: 12 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: 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.

Publications

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.
PubMed 32210440
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.
PubMed 31995602
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.
PubMed 30963691
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.
PubMed 26632545

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma

All Carcinoma, Hepatocellular trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT01246986
Acronym / sponsor ID: 13665
Conditions: Carcinoma, Hepatocellular
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 204 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: 30 Mar 2011 (actual)
Primary completion: 6 Jun 2019 (actual)
Study completion: 24 Dec 2019 (actual)
First posted: 24 Nov 2010 (estimated)
Results: Posted 7 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 7

Arm	Type	Receives
Part A Cohort 1-160 milligram (mg) LY2157299	Experimental	Drug: LY2157299Per 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.
Part A Cohort 2 - 300 mg LY2157299	Experimental	Drug: LY2157299, Drug: Sorafenib150 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.
Part B - 300 mg LY2157299	Experimental	Drug: LY2157299150 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.
Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib	Experimental	Drug: LY2157299, Drug: Sorafenib80 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.
Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib	Experimental	Drug: LY2157299, Drug: Sorafenib150 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.
Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab	Experimental	Drug: LY2157299, Drug: Ramucirumab80 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.
Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab	Experimental	Drug: LY2157299, Drug: Ramucirumab150 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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

Key exclusion criteria (18 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LY2157299Administered orally	Drug	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
SorafenibAdministered orally	Drug	Part A Cohort 2 - 300 mg LY2157299, Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib, Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib
RamucirumabAlso: LY30098016Administered IV	Drug	Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab, Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab

Primary outcome

Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)
Time frame: Baseline, discontinuation from any cause (Up to 83 months)
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)
Time frame: Baseline,discontinuation from any cause (Up to 83 months)
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)
Time frame: Randomization to date of first measured progressive disease (Up to 36 Weeks)
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.

9 secondary outcomes

Population Pharmacokinetics (PK) Mean Population Clearance 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
Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials
Time frame: Cycle 1 (28 Days)
Overall Survival (OS)
Time frame: Randomization to date of death from any cause (Up to 83 months)
Progression Free Survival (PFS)
Time frame: Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)
Percentage of Participants Achieving an Objective Response (Response Rate)
Time frame: Randomization to measured progressive disease (Up to 36 Weeks)
Duration of Tumor Response (DoR)
Time frame: Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)
Time to Treatment Failure (TTF)
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)
Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score
Time frame: Baseline, Day 1 Cycle 4
Time to Worsening (TTW) of Symptoms (FACT-Hep)
Time frame: Baseline to the worsening of symptoms (up to 567 days)

Results and safety

Results posted to the registry on 7 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A Cohort 1 - 160 mg LY2157299	37	34
Part A Cohort 2 - 300 mg LY2157299	72	67
Part B - 300 mg LY2157299	40	34
Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	3	3
Part C Cohort 2 - 300 mg LY2157299 + Sorafenib	44	40
Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab	3	2
Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab	5	5

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

Time frame: Baseline, discontinuation from any cause (Up to 83 months). Median (95% Confidence Interval). Unit: Months

Measure	Part A Cohort 1 - 160 mg LY2157299 n = 8	Part A Cohort 2 - 300 mg LY2157299 n = 14	Part B LY2157299 n = 10	Part C LY2157299 n = 27
Value	19.0 (1.5 to 25.1)	21.5 (2.9 to 34.2)	24.2 (3.0 to NA)	17.9 (12.6 to 32.8)

Population analysed: All participants who received at least one dose of study drug, achieved a \>20% reduction in biomarker AFP, and had evaluable post-baseline biomarker data. Due to low enrollment into Part C Cohort - 160 mg reporting group, Kaplan Meier analysis for OS was not conducted in this subgroup. Per protocol, Part D collected safety data only.

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

Time frame: Baseline,discontinuation from any cause (Up to 83 months). Median (95% Confidence Interval). Unit: Months

Measure	Part A Cohort 1 - 160 mg LY2157299 n = 16	Part A Cohort 2 - 300 mg LY2157299 n = 34	Part B LY2157299 n = 28	Part C LY2157299 n = 31
Value	11.9 (5.4 to 15.6)	10.1 (4.9 to 15.5)	21.9 (12.4 to NA)	22.88 (16.2 to 31.8)

Population analysed: All participants who received at least one dose of study drug, achieved a \>20% reduction in biomarker TGF-β and had evaluable post-baseline biomarker data. Due to low enrollment in Part C Cohort 1 - 160 mg reporting group, Kaplan Meier analysis for OS was not conducted in this subgroup. Per protocol, Part D collected safety data only.

Primary outcome: Time to Progression (TTP)

Time frame: Randomization to date of first measured progressive disease (Up to 36 Weeks). Median (90% Confidence Interval). Unit: Weeks

Measure	Part A Cohort 1 - 160 mg LY2157299 n = 37	Part A Cohort 2 - 300 mg LY2157299 n = 72	Part B - 300 mg LY2157299 n = 40	Part C Cohort 1 - 160 mg + Sorafenib n = 3	Part C Cohort 2 - 300 mg LY2157299 + Sorafenib n = 44
Value	12.1 (6.3 to 17.6)	7.1 (6.3 to 12.7)	18.0 (10.0 to 24.0)	36.0 (18.0 to 36.0)	17.9 (12.1 to 24.0)

Population analysed: All participants who receive at least one dose of study drug. Per protocol, Part D collected safety data only.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to 41.5 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A Cohort 1 - 160 mg LY2157299	15 of 37 (40.5%)	32 of 37 (86.5%)	33 of 37
Part A Cohort 2 - 300 mg LY2157299	36 of 72 (50%)	64 of 72 (88.9%)	63 of 72
Part B - 300 mg LY2157299	16 of 40 (40%)	38 of 40 (95%)	26 of 40
Part C Cohort 1 - 160 mg LY2157299 + Sorafenib	3 of 3 (100%)	3 of 3 (100%)	3 of 3
Part C Cohort 2 - 300 mg LY2157299 + Sorafenib	28 of 44 (63.6%)	44 of 44 (100%)	36 of 44
Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab	1 of 3 (33.3%)	3 of 3 (100%)	2 of 3
Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab	2 of 5 (40%)	5 of 5 (100%)	5 of 5

Limitations and caveats (from the sponsor): Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm. Per protocol, Part D collected safety data only.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32210440Giannelli 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.
Derived from this study: PubMed 31995602Addepalli 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.
Derived from this study: PubMed 30963691Faivre 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.
Derived from this study: PubMed 26632545Li S, Yang F, Ren X. Immunotherapy for hepatocellular carcinoma. Drug Discov Ther. 2015 Oct;9(5):363-71. doi: 10.5582/ddt.2015.01054.
A Study of LY2157299 in Participants With Hepatocellular CarcinomaLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

Related trials for Carcinoma, Hepatocellular

RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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) study director

Eli Lilly and Company

40 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LY2157299, Sorafenib and Ramucirumab in people with Carcinoma, Hepatocellular, run by Eli Lilly and Company at 40 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in France, United States, Germany, Australia, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS) (time frame: Baseline, discontinuation from any cause (Up to 83 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01246986, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2021.