A Study of LY2157299 in Participants With Hepatocellular Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01246986
First received: November 1, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to estimate the median time to progression in participants with hepatocellular carcinoma (HCC) when treated with LY2157299 with or without Sorafenib


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: LY2157299
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Relationship of change in response biomarker to clinical benefit [ Time Frame: Baseline through discontinuation from any cause ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Randomization to date of first measured progressive disease ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Population pharmacokinetics [ Time Frame: Baseline through cycle 1 ] [ Designated as safety issue: No ]
  • Recommended dose for phase 3 HCC trials [ Time Frame: Baseline to end of study ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Randomization to date of death from any cause ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: Randomization to measured progressive disease or death from any cause ] [ Designated as safety issue: No ]
  • Proportion of participants achieving an objective response (response rate) [ Time Frame: Randomization to measured progressive disease ] [ Designated as safety issue: No ]
  • Duration of tumor response [ Time Frame: Time of response to measured progressive disease or death from any cause ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause ] [ Designated as safety issue: No ]
  • Change from baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) sub-scores and total score [ Time Frame: Baseline through the end of the study ] [ Designated as safety issue: Yes ]
  • Time to worsening of symptoms (FACT-Hep) [ Time Frame: Baseline through the end of the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 190
Study Start Date: March 2011
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 160 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.

160 mg LY2157299 given daily for 14 days followed by 14 days of rest. This on/off schedule constitutes a cycle of 28 days. Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Drug: LY2157299
Administered orally
Experimental: 300 mg LY2157299
300 mg LY2157299 given daily for 14 days followed by 14 days of rest. This on/off schedule constitutes a cycle of 28 days. Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Drug: LY2157299
Administered orally
Experimental: 160 mg LY2157299 + 800 mg Sorafenib
During each 28-day cycle: 160 mg LY2157299 given daily for 14 days followed by 14 days of rest. 800 mg Sorafenib will be given daily for 28 days. Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Drug: Sorafenib
Administered orally
Experimental: 300 mg LY2157299 + 800 mg Sorafenib
During each 28-day cycle: 300 mg LY2157299 given daily for 14 days followed by 14 days of rest. 800 mg Sorafenib will be given daily for 28 days. Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Drug: Sorafenib
Administered orally

Detailed Description:

The study consists of three Parts: Part A where HCC participants with an increased alpha feto protein (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 and Part C where treatment-naïve HCC participants will be treated with 160 mg LY2157299 + Sorafenib or 300 mg LY2157299 + Sorafenib.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Child-Pugh Stage: A or B7 for Parts A & B, A for Part C
  • 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
  • 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 ascitis
  • 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
  • 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. For additional details
    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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01246986

Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, California
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. Recruiting
San Francisco, California, United States, 94115
Contact: Eli Lilly         
United States, District of Columbia
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. Recruiting
Washington, District of Columbia, United States, 20007
Contact: Eli Lilly         
United States, Illinois
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. Recruiting
Chicago, Illinois, United States, 60611
Contact: Eli Lilly         
United States, New York
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. Recruiting
New York, New York, United States, 10021
Contact: Eli Lilly         
Australia, Western 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. Active, not recruiting
Nedlands, Western Australia, Australia, 6009
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. Recruiting
Caen, France, 14033
Contact: Eli Lilly         
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. Recruiting
Clichy, France, 92118
Contact: Eli Lilly         
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. Active, not recruiting
Creteil, France, 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. Active, not recruiting
Lille, France, 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. Recruiting
Lyon, France, 69317
Contact: Eli Lilly         
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. Recruiting
Pessac, France, 33604
Contact: Eli Lilly         
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. Active, not recruiting
Saint Herblain, France, 44800
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. Active, not recruiting
Vandoeuvre Les Nancy, France, 54511
Germany
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. Recruiting
Erlangen, Germany, 91054
Contact: Eli Lilly         
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. Recruiting
Mainz, Germany, 55131
Contact: Eli Lilly         
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. Recruiting
Bari, Italy, 70124
Contact: Eli Lilly         
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. Active, not recruiting
Rome, Italy, 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. Active, not recruiting
Rozzano, Italy, 20089
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. Recruiting
Grafton, New Zealand, 1023
Contact: Eli Lilly         
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. Active, not recruiting
Madrid, Spain, 28007
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01246986     History of Changes
Other Study ID Numbers: 13665, H9H-MC-JBAK
Study First Received: November 1, 2010
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014