A Study of LY2157299 in Participants With Hepatocellular Carcinoma
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: LY2157299; Sorafenib; Ramucirumab
Intervention description: Administered orally; Administered orally; Administered IV
Intervention MeSH terms: Sorafenib; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 204.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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