A Study of LY2157299 in Participants With Hepatocellular Carcinoma

NCT ID: NCT01246986

Last Updated: 2021-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-30
• Study Completion Date: 2019-12-24

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A Cohort 1-160 milligram (mg) LY2157299

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

Part A Cohort 2 - 300 mg LY2157299

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

Sorafenib

Intervention Type: DRUG

Administered orally

Part B - 300 mg LY2157299

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

Sorafenib

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

Sorafenib

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

Ramucirumab

Intervention Type: DRUG

Administered IV

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

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.

Group Type: EXPERIMENTAL

LY2157299

Intervention Type: DRUG

Administered orally

Ramucirumab

Intervention Type: DRUG

Administered IV

Interventions

LY2157299

Administered orally

Intervention Type: DRUG

Sorafenib

Administered orally

Intervention Type: DRUG

Ramucirumab

Administered IV

Intervention Type: DRUG

Other Intervention Names

LY30098016

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:

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

University of California, San Francisco

San Francisco, California, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

MD Anderson Cancer Center Orlando

Orlando, Florida, United States

Northwestern University

Chicago, Illinois, United States

Indiana Univ Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

Lahey Clinic Medical Center

Burlington, Massachusetts, United States

Weill Cornell Medical College

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

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, Australia

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, , Australia

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Heidelberg, , Australia

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St Leonards, , Australia

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Brest, , France

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Caen, , France

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Clichy, , France

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Créteil, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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, , France

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Paris, , France

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, , France

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Saint-Etienne, , France

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Saint-Herblain, , France

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Strasbourg, , France

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Vandœuvre-lès-Nancy, , France

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Berlin, , Germany

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Cologne, , Germany

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Erlangen, , Germany

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Göttingen, , Germany

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Mainz, , Germany

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Münster, , Germany

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Bari, , Italy

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Rome, , Italy

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, , Italy

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, , New Zealand

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, , Spain

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, , Spain

Countries

United States; Australia; France; Germany; Italy; New Zealand; Spain

References

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.

Reference Type: DERIVED

PMID: 32210440 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31995602 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30963691 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26632545 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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

A Study of LY2157299 in Participants With Hepatocellular Carcinoma

Other Identifiers

H9H-MC-JBAK

Identifier Type: OTHER

Identifier Source: secondary_id

2010-022338-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13665

Identifier Type: -

Identifier Source: org_study_id