Conditions

Hepatocellular Carcinoma

Keywords

transforming growth factor beta (TGF-β)

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS): Number of Events
OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported.
Randomization to Date of Death from Any Cause (Up To 24 Months)

Secondary Outcomes (7)

Population Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib
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
Population Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib
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
Time to Tumor Progression (TTP)
Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up To 24 Months)
Progression-Free Survival (PFS)
Randomization to Measured Progressive Disease or Death (Up To 24 Months)
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Randomization to Measured Progressive Disease (Up To 24 Months)
+2 more secondary outcomes

Study Arms (3)

150 milligram (mg) Galunisertib Monotherapy

EXPERIMENTAL

150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle).

Drug: LY2157299

150 mg Galunisertib + 400 mg Sorafenib Therapy

EXPERIMENTAL

150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Drug: LY2157299Drug: Sorafenib

400 mg Sorafenib + Placebo Therapy

PLACEBO COMPARATOR

Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days.

Drug: SorafenibDrug: Placebo

Interventions

LY2157299DRUG

Administered orally

150 mg Galunisertib + 400 mg Sorafenib Therapy150 milligram (mg) Galunisertib Monotherapy

SorafenibDRUG

Administered orally

150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy

PlaceboDRUG

Administered orally

400 mg Sorafenib + Placebo Therapy

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Have histological evidence of a diagnosis of HCC not amenable to curative surgery.
Have Child-Pugh Class A.
Have the presence of measurable disease.
Have adequate organ function.
Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
If male or female 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.
If females with childbearing potential, must have had a negative serum pregnancy test 7 days prior to the first dose of study drug.
Are able to swallow capsules or tablets.
Have available diagnostic or biopsy tumor tissue.

You may not qualify if:

Have received previous systemic treatment for advanced disease.
Have known HCC with fibro-lamellar or mixed histology.
Have presence of clinically relevant ascites.
Have had a liver transplant.
Have moderate or severe cardiac disease.
Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.
Have experienced Grade 3 or 4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention.
Have esophageal or gastric varices that require immediate intervention or represent a high bleeding risk.
Had major surgery within 4 weeks prior to the study randomization.

Contact the study team to confirm eligibility.