A Study of LY2157299 in Participants With Advanced Hepatocellular Carcinoma

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02178358
Collaborator
(none)
132
Enrollment
16
Locations
3
Arms
78.4
Actual Duration (Months)
8.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2157299 in participants with hepatocellular carcinoma.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
132 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase 2 Study of LY2157299 Versus LY2157299 - Sorafenib Combination Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Actual Study Start Date :
Aug 8, 2014
Actual Primary Completion Date :
Jun 30, 2017
Actual Study Completion Date :
Feb 18, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: 150 milligram (mg) Galunisertib Monotherapy

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

Drug: LY2157299
Administered orally

Experimental: 150 mg Galunisertib + 400 mg Sorafenib Therapy

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: LY2157299
Administered orally

Drug: Sorafenib
Administered orally

Placebo Comparator: 400 mg Sorafenib + Placebo Therapy

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: Sorafenib
Administered orally

Drug: Placebo
Administered orally

Outcome Measures

Primary Outcome Measures

  1. Overall Survival (OS): Number of Events [Randomization to Date of Death from Any Cause (Up To 24 Months)]

    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.

Secondary Outcome Measures

  1. 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 mean (between-subject coefficient variance [CV %]) apparent clearance.

  2. 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]

    Population Vss [distribution of galunisertib in the body at steady state] after a single dose of galunisertib.

  3. 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)]

    TTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  4. Progression-Free Survival (PFS) [Randomization to Measured Progressive Disease or Death (Up To 24 Months)]

    PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

  5. Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [Randomization to Measured Progressive Disease (Up To 24 Months)]

    ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.

  6. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score [Baseline, 24 Months]

    EORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much). Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.

  7. Change From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score [Baseline, 24 Months]

    The EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • 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.

Exclusion Criteria:
  • 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.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1For 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.BeijingChina100036
2For 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.BengbuChina233004
3For 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.ChangchunChina130012
4For 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.HangzhouChina310016
5For 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.HefeiChina230022
6For 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.Hong KongHong Kong
7For 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.KowloonHong Kong
8For 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.IncheonKorea, Republic of405-760
9For 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.SeoulKorea, Republic of135 720
10For 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.Gwei Shan TownshipTaiwan333
11For 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.Liouying/TainanTaiwan736
12For 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.Puzih CityTaiwan613
13For 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.TainanTaiwan70403
14For 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.TaipeiTaiwan11217
15For 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.TaoyuanTaiwan33378
16For 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.BangkokThailand10330

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 - hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02178358
Other Study ID Numbers:
  • 15065
  • H9H-MC-JBAS
First Posted:
Jun 30, 2014
Last Update Posted:
May 19, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment DetailIn the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment.
Arm/Group Title150 Milligram (mg) Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Period Title: Overall Study
STARTED207438
Received at Least 1 Dose of Study Drug207438
COMPLETED207134
NOT COMPLETED034

Baseline Characteristics

Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo TherapyTotal
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.Total of all reporting groups
Overall Participants207438132
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
13
65%
55
74.3%
28
73.7%
96
72.7%
>=65 years
7
35%
19
25.7%
10
26.3%
36
27.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
60.6
(7.8)
59.0
(8.5)
58.6
(11.8)
59.1
(9.4)
Sex: Female, Male (Count of Participants)
Female
4
20%
12
16.2%
1
2.6%
17
12.9%
Male
16
80%
62
83.8%
37
97.4%
115
87.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
20
100%
74
100%
38
100%
132
100%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
0
0%
White
0
0%
0
0%
0
0%
0
0%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
South Korea
7
35%
33
44.6%
13
34.2%
53
40.2%
Hong Kong
6
30%
10
13.5%
6
15.8%
22
16.7%
China
0
0%
15
20.3%
8
21.1%
23
17.4%
Taiwan
7
35%
11
14.9%
9
23.7%
27
20.5%
Thailand
0
0%
5
6.8%
2
5.3%
7
5.3%
Weight (kilogram (kg)) [Median (Full Range) ]
Median (Full Range) [kilogram (kg)]
66.400
63.575
62.400
63.575
Height (Centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeter (cm)]
162.84
(7.38)
165.30
(7.50)
166.55
(5.69)
165.29
(7.05)
BMI (kilogram per square metre (kg/m2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square metre (kg/m2)]
24.806
(4.105)
23.224
(3.248)
22.843
(3.062)
23.354
(3.373)
Tobacco use (Count of Participants)
Never
7
35%
28
37.8%
11
28.9%
46
34.8%
Former
7
35%
35
47.3%
22
57.9%
64
48.5%
Current
6
30%
11
14.9%
5
13.2%
22
16.7%
Alcohol use (Count of Participants)
Never
7
35%
29
39.2%
16
42.1%
52
39.4%
Former
0
0%
1
1.4%
2
5.3%
3
2.3%
Current
13
65%
44
59.5%
20
52.6%
77
58.3%
Alcohol drinks per week (Standard alcohol drinks per week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Standard alcohol drinks per week]
5.7
(7.2)
3.3
(4.7)
2.3
(2.8)
3.4
(4.8)

Outcome Measures

1. Primary Outcome
TitleOverall Survival (OS): Number of Events
DescriptionOS 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.
Time FrameRandomization to Date of Death from Any Cause (Up To 24 Months)

Outcome Measure Data

Analysis Population Description
All randomized participants. Censored participants: Galunisertib Monotherapy =5, Galunisertib Plus Sorafenib Therapy = 16 and Sorafenib Plus Placebo Therapy = 7.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Measure Participants207438
Number [Participants with events]
15
75%
58
78.4%
31
81.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Galunisertib Monotherapy, 400 mg Sorafenib + Placebo Therapy
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.837
Comments
MethodBayesian exponential-likelihood model
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.776
Confidence Interval (2-Sided) 95%
0.434 to 1.226
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 150 mg Galunisertib + 400 mg Sorafenib Therapy, 400 mg Sorafenib + Placebo Therapy
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.704
Comments
MethodBayesian exponential-likelihood model
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.917
Confidence Interval (2-Sided) 95%
0.633 to 1.266
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
TitlePopulation Pharmacokinetics (PopPK): Mean Population Clearance of Galunisertib
DescriptionPopulation mean (between-subject coefficient variance [CV %]) apparent clearance.
Time FrameCycle (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

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK.
Arm/Group TitleGalunisertib Monotherapy and Galunisertib + Sorafenib Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 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.
Measure Participants91
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour (L/hr)]
33.6
(48)
3. Secondary Outcome
TitlePopulation Pharmacokinetics (PopPK): Steady State Apparent Volume of Distribution (Vss) of Galunisertib
DescriptionPopulation Vss [distribution of galunisertib in the body at steady state] after a single dose of galunisertib.
Time FrameCycle (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

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least one dose of study drug, with evaluable galunisertib PK data. The analyses conducted on galunisertib exposure parameter from both arms combined per the statistical analysis plan, as monotherapy and combination arm showed no difference in galunisertib PK.
Arm/Group TitleGalunisertib Monotherapy and Galunisertib + Sorafenib Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 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.
Measure Participants91
Geometric Mean (Geometric Coefficient of Variation) [Liters (L)]
192
(69)
4. Secondary Outcome
TitleTime to Tumor Progression (TTP)
DescriptionTTP at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time FrameRandomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up To 24 Months)

Outcome Measure Data

Analysis Population Description
All randomized participants. Censored participants: Galunisertib Monotherapy =2, Galunisertib Plus Sorafenib Therapy = 15 and Sorafenib Plus Placebo Therapy = 9.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Measure Participants207438
Median (95% Confidence Interval) [Months]
1.41
2.86
4.14
5. Secondary Outcome
TitleProgression-Free Survival (PFS)
DescriptionPFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Time FrameRandomization to Measured Progressive Disease or Death (Up To 24 Months)

Outcome Measure Data

Analysis Population Description
All randomized participants. Censored participants: Galunisertib Monotherapy =1, Galunisertib Plus Sorafenib Therapy = 8 and Sorafenib Plus Placebo Therapy = 5.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Measure Participants207438
Median (99% Confidence Interval) [Months]
1.41
2.86
4.14
6. Secondary Outcome
TitlePercentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
DescriptionORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Time FrameRandomization to Measured Progressive Disease (Up To 24 Months)

Outcome Measure Data

Analysis Population Description
All randomized participants.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Measure Participants207438
Number (95% Confidence Interval) [Percentage of participants]
0.05
0.3%
0.027
0%
0.158
0.4%
7. Secondary Outcome
TitleChange From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Score
DescriptionEORTC QLQ-C30 consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much). Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.
Time FrameBaseline, 24 Months

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least one dose of study drug and with baseline and post-baseline EORTC QLQ-C30 data for each EORTC QLQ-C30 items.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Measure Participants196535
Global health status
43.42
(23.171)
55.90
(22.473)
58.57
(17.326)
Functional scale: Physical functioning
84.56
(16.338)
82.87
(19.613)
80.95
(16.580)
Functional scale: Role functioning
89.47
(14.918)
82.05
(24.880)
85.24
(19.289)
Functional Scale: Emotional Functioning
84.65
(18.271)
87.18
(17.247)
86.90
(13.898)
Functional Scale: Cognitive Functioning
89.47
(16.860)
91.03
(14.754)
85.71
(18.142)
Functional Scale: Social Functioning
83.33
(24.845)
84.10
(19.859)
84.29
(18.052)
Symptom Scale: Fatigue
21.05
(23.393)
24.10
(22.444)
25.40
(18.390)
Symptom Scale: Nausea and Vomiting
2.63
(8.358)
3.85
(8.725)
3.33
(8.856)
Symptom scale: Pain
17.54
(19.621)
17.18
(25.340)
14.76
(20.521)
Symptom scale: Dyspnoea
17.54
(28.040)
11.79
(19.922)
12.38
(18.232)
Symptom scale: Insomnia
21.05
(31.838)
9.74
(19.296)
16.19
(16.903)
Symptom scale: Appetite loss
15.79
(25.744)
16.92
(25.768)
18.10
(23.351)
Symptom scale: Constipation
5.26
(12.488)
6.15
(13.033)
6.67
(15.760)
Symptom scale: Diarrhoea
10.53
(19.413)
4.62
(13.013)
10.48
(17.660)
Symptom scale: Financial difficulties
15.79
(25.744)
23.08
(26.954)
20.95
(22.989)
8. Secondary Outcome
TitleChange From Baseline in EORTC QLQ Hepatocellular Carcinoma (HCC-18) Questionnaire Score
DescriptionThe EORTC QLQ-HCC-18 was an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30. EORTC QLQ-HCC 18 questionnaire included 8 symptom scales such as abdominal swelling, sex life, fatigue, body image, jaundice, nutrition, pain and fever. Each individual item ranges from 1 to 4, where 1 = "not at all" and 4 = "very much." All domain scores were calculated as an average of item scores and transformed to 0 to 100 score range. A high score for a symptom scale/item represented a high level of symptomatology/problem.
Time FrameBaseline, 24 Months

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC-QLQ HCC-18 data for each EORTC-QLQ HCC-18 items.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
Measure Participants196535
Abdominal swelling
24.56
(33.040)
32.82
(31.453)
27.62
(24.899)
Sex Life
28.07
(31.940)
58.97
(35.242)
46.08
(35.783)
Fatigue
32.16
(21.563)
47.86
(29.128)
46.98
(26.278)
Body Image
28.07
(26.089)
36.15
(22.930)
31.90
(20.758)
Jaundice
20.18
(25.202)
27.69
(25.392)
25.24
(21.531)
Nutrition
22.46
(21.223)
34.05
(23.456)
34.48
(18.611)
Pain
25.44
(18.732)
25.38
(21.471)
30.95
(21.822)
Fever
14.04
(16.909)
25.38
(25.019)
20.48
(20.646)

Adverse Events

Time FrameUp To 24 Months
Adverse Event Reporting Description All randomized participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Arm/Group Title150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Arm/Group Description150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle).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.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.
All Cause Mortality
150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total15/20 (75%) 58/74 (78.4%) 31/38 (81.6%)
Serious Adverse Events
150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total6/20 (30%) 31/74 (41.9%) 11/38 (28.9%)
Blood and lymphatic system disorders
Anaemia0/20 (0%) 02/74 (2.7%) 20/38 (0%) 0
Febrile neutropenia0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Leukopenia0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Lymphadenopathy0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Cardiac disorders
Myocardial infarction0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Ear and labyrinth disorders
Hearing impaired1/20 (5%) 10/74 (0%) 00/38 (0%) 0
Vertigo0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Gastrointestinal disorders
Abdominal distension0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Abdominal pain0/20 (0%) 03/74 (4.1%) 42/38 (5.3%) 2
Ascites0/20 (0%) 02/74 (2.7%) 21/38 (2.6%) 2
Diarrhoea0/20 (0%) 02/74 (2.7%) 21/38 (2.6%) 1
Duodenal ulcer haemorrhage0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Food poisoning0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Gastritis0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Gastritis haemorrhagic0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Gastrointestinal haemorrhage0/20 (0%) 02/74 (2.7%) 20/38 (0%) 0
Haematochezia0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Haemorrhoidal haemorrhage1/20 (5%) 30/74 (0%) 00/38 (0%) 0
Haemorrhoids0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Nausea0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Oesophageal varices haemorrhage1/20 (5%) 13/74 (4.1%) 30/38 (0%) 0
Rectal haemorrhage0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Upper gastrointestinal haemorrhage0/20 (0%) 04/74 (5.4%) 40/38 (0%) 0
Varices oesophageal0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
General disorders
Chest pain0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Fatigue0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Oedema peripheral0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Pyrexia0/20 (0%) 04/74 (5.4%) 60/38 (0%) 0
Hepatobiliary disorders
Cholangitis0/20 (0%) 00/74 (0%) 01/38 (2.6%) 2
Hepatic failure0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Hepatic haemorrhage0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Jaundice1/20 (5%) 10/74 (0%) 00/38 (0%) 0
Infections and infestations
Anal infection0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Biliary tract infection0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Cellulitis0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Endocarditis bacterial0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Influenza0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Oesophageal candidiasis0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Pneumonia1/20 (5%) 11/74 (1.4%) 11/38 (2.6%) 1
Sepsis1/20 (5%) 10/74 (0%) 00/38 (0%) 0
Streptococcal sepsis0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Injury, poisoning and procedural complications
Hepatic rupture0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Investigations
Blood bilirubin increased0/20 (0%) 00/74 (0%) 01/38 (2.6%) 2
Platelet count decreased0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Troponin i increased0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Metabolism and nutrition disorders
Hypoalbuminaemia0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Hypoglycaemia1/20 (5%) 10/74 (0%) 00/38 (0%) 0
Musculoskeletal and connective tissue disorders
Neck pain1/20 (5%) 10/74 (0%) 00/38 (0%) 0
Nervous system disorders
Cerebral haemorrhage0/20 (0%) 01/74 (1.4%) 11/38 (2.6%) 1
Dizziness0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Haemorrhage intracranial0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Hepatic encephalopathy1/20 (5%) 11/74 (1.4%) 10/38 (0%) 0
Renal and urinary disorders
Azotaemia0/20 (0%) 00/74 (0%) 01/38 (2.6%) 1
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration1/20 (5%) 10/74 (0%) 00/38 (0%) 0
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Rash maculo-papular0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Urticaria0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Vascular disorders
Shock0/20 (0%) 01/74 (1.4%) 10/38 (0%) 0
Other (Not Including Serious) Adverse Events
150 mg Galunisertib Monotherapy150 mg Galunisertib + 400 mg Sorafenib Therapy400 mg Sorafenib + Placebo Therapy
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total17/20 (85%) 73/74 (98.6%) 38/38 (100%)
Blood and lymphatic system disorders
Anaemia2/20 (10%) 317/74 (23%) 267/38 (18.4%) 7
Thrombocytopenia0/20 (0%) 01/74 (1.4%) 23/38 (7.9%) 3
Cardiac disorders
Palpitations0/20 (0%) 01/74 (1.4%) 12/38 (5.3%) 2
Endocrine disorders
Hyperthyroidism0/20 (0%) 00/74 (0%) 02/38 (5.3%) 2
Gastrointestinal disorders
Abdominal distension6/20 (30%) 68/74 (10.8%) 104/38 (10.5%) 5
Abdominal pain5/20 (25%) 616/74 (21.6%) 187/38 (18.4%) 7
Abdominal pain upper1/20 (5%) 11/74 (1.4%) 14/38 (10.5%) 6
Ascites3/20 (15%) 36/74 (8.1%) 64/38 (10.5%) 4
Constipation2/20 (10%) 310/74 (13.5%) 117/38 (18.4%) 10
Diarrhoea5/20 (25%) 829/74 (39.2%) 5122/38 (57.9%) 50
Dyspepsia2/20 (10%) 27/74 (9.5%) 91/38 (2.6%) 1
Nausea1/20 (5%) 114/74 (18.9%) 154/38 (10.5%) 4
Stomatitis0/20 (0%) 07/74 (9.5%) 1010/38 (26.3%) 13
Toothache0/20 (0%) 01/74 (1.4%) 12/38 (5.3%) 3
Vomiting2/20 (10%) 215/74 (20.3%) 194/38 (10.5%) 8
General disorders
Asthenia0/20 (0%) 01/74 (1.4%) 12/38 (5.3%) 2
Chills1/20 (5%) 11/74 (1.4%) 12/38 (5.3%) 2
Fatigue6/20 (30%) 823/74 (31.1%) 2814/38 (36.8%) 16
Influenza like illness2/20 (10%) 37/74 (9.5%) 81/38 (2.6%) 2
Malaise0/20 (0%) 04/74 (5.4%) 63/38 (7.9%) 4
Mucosal inflammation0/20 (0%) 04/74 (5.4%) 41/38 (2.6%) 1
Non-cardiac chest pain1/20 (5%) 11/74 (1.4%) 12/38 (5.3%) 2
Oedema0/20 (0%) 00/74 (0%) 02/38 (5.3%) 2
Oedema peripheral2/20 (10%) 24/74 (5.4%) 46/38 (15.8%) 6
Pain1/20 (5%) 14/74 (5.4%) 41/38 (2.6%) 1
Pyrexia1/20 (5%) 326/74 (35.1%) 435/38 (13.2%) 5
Infections and infestations
Rash pustular1/20 (5%) 14/74 (5.4%) 43/38 (7.9%) 3
Upper respiratory tract infection0/20 (0%) 02/74 (2.7%) 25/38 (13.2%) 6
Investigations
Alanine aminotransferase increased2/20 (10%) 223/74 (31.1%) 4015/38 (39.5%) 24
Aspartate aminotransferase increased2/20 (10%) 226/74 (35.1%) 4215/38 (39.5%) 25
Blood alkaline phosphatase increased0/20 (0%) 010/74 (13.5%) 123/38 (7.9%) 4
Blood bilirubin increased2/20 (10%) 211/74 (14.9%) 1515/38 (39.5%) 22
Blood creatine phosphokinase increased0/20 (0%) 05/74 (6.8%) 83/38 (7.9%) 9
Blood lactate dehydrogenase increased0/20 (0%) 08/74 (10.8%) 123/38 (7.9%) 3
Gamma-glutamyltransferase increased0/20 (0%) 09/74 (12.2%) 95/38 (13.2%) 7
Lipase increased0/20 (0%) 01/74 (1.4%) 12/38 (5.3%) 5
Lymphocyte count decreased0/20 (0%) 04/74 (5.4%) 51/38 (2.6%) 1
Neutrophil count decreased1/20 (5%) 19/74 (12.2%) 144/38 (10.5%) 4
Platelet count decreased0/20 (0%) 019/74 (25.7%) 3513/38 (34.2%) 21
Thyroxine increased0/20 (0%) 00/74 (0%) 02/38 (5.3%) 2
Weight decreased2/20 (10%) 25/74 (6.8%) 66/38 (15.8%) 6
White blood cell count decreased0/20 (0%) 04/74 (5.4%) 65/38 (13.2%) 10
Metabolism and nutrition disorders
Decreased appetite3/20 (15%) 327/74 (36.5%) 2812/38 (31.6%) 15
Hyperglycaemia2/20 (10%) 22/74 (2.7%) 52/38 (5.3%) 3
Hypoalbuminaemia1/20 (5%) 17/74 (9.5%) 79/38 (23.7%) 10
Hypocalcaemia0/20 (0%) 06/74 (8.1%) 65/38 (13.2%) 7
Hypokalaemia1/20 (5%) 110/74 (13.5%) 164/38 (10.5%) 6
Hypomagnesaemia0/20 (0%) 01/74 (1.4%) 16/38 (15.8%) 9
Hyponatraemia1/20 (5%) 15/74 (6.8%) 67/38 (18.4%) 10
Hypophosphataemia2/20 (10%) 233/74 (44.6%) 7413/38 (34.2%) 23
Musculoskeletal and connective tissue disorders
Arthralgia1/20 (5%) 12/74 (2.7%) 22/38 (5.3%) 2
Back pain1/20 (5%) 13/74 (4.1%) 33/38 (7.9%) 3
Musculoskeletal pain0/20 (0%) 02/74 (2.7%) 34/38 (10.5%) 4
Myalgia0/20 (0%) 02/74 (2.7%) 24/38 (10.5%) 4
Nervous system disorders
Dizziness0/20 (0%) 05/74 (6.8%) 54/38 (10.5%) 7
Headache3/20 (15%) 37/74 (9.5%) 81/38 (2.6%) 1
Peripheral sensory neuropathy0/20 (0%) 00/74 (0%) 02/38 (5.3%) 2
Psychiatric disorders
Insomnia1/20 (5%) 16/74 (8.1%) 63/38 (7.9%) 3
Renal and urinary disorders
Proteinuria1/20 (5%) 17/74 (9.5%) 106/38 (15.8%) 9
Reproductive system and breast disorders
Genital disorder female0/4 (0%) 01/12 (8.3%) 10/1 (0%) 0
Genital rash0/20 (0%) 00/74 (0%) 02/38 (5.3%) 2
Respiratory, thoracic and mediastinal disorders
Cough3/20 (15%) 38/74 (10.8%) 96/38 (15.8%) 6
Dysphonia0/20 (0%) 06/74 (8.1%) 75/38 (13.2%) 5
Dyspnoea2/20 (10%) 26/74 (8.1%) 66/38 (15.8%) 6
Epistaxis0/20 (0%) 03/74 (4.1%) 33/38 (7.9%) 4
Haemoptysis0/20 (0%) 01/74 (1.4%) 13/38 (7.9%) 4
Oropharyngeal pain1/20 (5%) 14/74 (5.4%) 46/38 (15.8%) 7
Pleural effusion0/20 (0%) 01/74 (1.4%) 12/38 (5.3%) 2
Productive cough1/20 (5%) 11/74 (1.4%) 12/38 (5.3%) 3
Skin and subcutaneous tissue disorders
Alopecia0/20 (0%) 015/74 (20.3%) 157/38 (18.4%) 7
Dermatitis acneiform0/20 (0%) 013/74 (17.6%) 186/38 (15.8%) 7
Dry skin1/20 (5%) 12/74 (2.7%) 22/38 (5.3%) 2
Erythema0/20 (0%) 04/74 (5.4%) 41/38 (2.6%) 1
Erythema multiforme2/20 (10%) 20/74 (0%) 00/38 (0%) 0
Palmar-plantar erythrodysaesthesia syndrome4/20 (20%) 542/74 (56.8%) 5719/38 (50%) 25
Pruritus3/20 (15%) 313/74 (17.6%) 204/38 (10.5%) 5
Rash1/20 (5%) 120/74 (27%) 249/38 (23.7%) 10
Rash maculo-papular1/20 (5%) 17/74 (9.5%) 113/38 (7.9%) 4
Vascular disorders
Hypertension0/20 (0%) 015/74 (20.3%) 154/38 (10.5%) 4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period of less than 90 days from the time submitted to the sponsor for review.The PI will remove from publication the information which the sponsor reasonably thinks would jeopardize its intellectual property interests or delay the publication until the publication no longer jeopardizes its intellectual property interests.

Results Point of Contact

Name/TitleChief Medical Officer
OrganizationEli Lilly and Company
Phone800-545-5979
Emailclinicaltrials.gov@lilly.com
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02178358
Other Study ID Numbers:
  • 15065
  • H9H-MC-JBAS
First Posted:
Jun 30, 2014
Last Update Posted:
May 19, 2021
Last Verified:
Apr 1, 2021