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A Study of LY2157299 in Participants With Hepatocellular Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01246986
First received: November 1, 2010
Last updated: March 1, 2017
Last verified: March 2017
  Purpose
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.

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma

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 ]
  • Time to progression [ Time Frame: Randomization to date of first measured progressive disease ]

Secondary Outcome Measures:
  • Population pharmacokinetics [ Time Frame: Baseline through cycle 1 ]
  • Recommended dose for phase 3 HCC trials [ Time Frame: Baseline to end of study ]
  • Overall survival [ Time Frame: Randomization to date of death from any cause ]
  • Progression free survival [ Time Frame: Randomization to measured progressive disease or death from any cause ]
  • Proportion of participants achieving an objective response (response rate) [ Time Frame: Randomization to measured progressive disease ]
  • Duration of tumor response [ Time Frame: Time of response to measured progressive disease or death from any cause ]
  • 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 ]
  • 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 ]
  • Time to worsening of symptoms (FACT-Hep) [ Time Frame: Baseline through the end of the study ]

Estimated Enrollment: 235
Study Start Date: March 2011
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: November 2017 (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: LY2157299
Administered orally
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: LY2157299
Administered orally
Drug: Sorafenib
Administered orally
Experimental: 80 mg LY2157299 + 8 mg/kg Ramucirumab
During each 28-day cycle: 80 mg LY2157299 given twice a day for 14 days followed by 14 days of rest. 8 mg/kilogram (kg) ramucirumab will be given daily for 15 days. Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Drug: LY2157299
Administered orally
Drug: Ramucirumab
Administered IV
Other Name: LY30098016
Experimental: 150 mg LY2157299 + 8 mg/kg Ramucirumab
During each 28-day cycle: 150 mg LY2157299 given twice a day for 14 days followed by 14 days of rest. 8 mg/kg ramucirumab will be given daily for 15 days. Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.
Drug: LY2157299
Administered orally
Drug: Ramucirumab
Administered IV
Other Name: LY30098016

Detailed Description:

The study consists of four 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, 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 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 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 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
  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

  Show 40 Study Locations
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01246986     History of Changes
Other Study ID Numbers: 13665
H9H-MC-JBAK ( Other Identifier: Eli Lilly and Company )
2010-022338-10 ( EudraCT Number )
Study First Received: November 1, 2010
Last Updated: March 1, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.


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
Ramucirumab
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017