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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01246986




Registration number
NCT01246986
Ethics application status
Date submitted
1/11/2010
Date registered
24/11/2010

Titles & IDs
Public title
A Study of LY2157299 in Participants With Hepatocellular Carcinoma
Scientific title
Phase 2 Study of LY2157299 in Patients With Hepatocellular Carcinoma
Secondary ID [1] 0 0
H9H-MC-JBAK
Secondary ID [2] 0 0
13665
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY2157299
Treatment: Drugs - Sorafenib
Treatment: Drugs - Ramucirumab

Experimental: Part A Cohort 1-160 milligram (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.

80 mg LY2157299 given orally twice daily (BID) for 14 days followed by 14 days off (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Experimental: Part A Cohort 2 - 300 mg LY2157299 - 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Experimental: Part B - 300 mg LY2157299 - 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Experimental: Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib - 80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Experimental: Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib - 150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Experimental: Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab - 80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.

Experimental: Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab - 150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).

Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met.


Treatment: Drugs: LY2157299
Administered orally

Treatment: Drugs: Sorafenib
Administered orally

Treatment: Drugs: Ramucirumab
Administered IV

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)
Timepoint [1] 0 0
Baseline, discontinuation from any cause (Up to 83 months)
Primary outcome [2] 0 0
Change From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-ß) to Overall Survival (OS)
Timepoint [2] 0 0
Baseline,discontinuation from any cause (Up to 83 months)
Primary outcome [3] 0 0
Time to Progression (TTP)
Timepoint [3] 0 0
Randomization to date of first measured progressive disease (Up to 36 Weeks)
Secondary outcome [1] 0 0
Population Pharmacokinetics (PK) Mean Population Clearance of Galunisertib
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials
Timepoint [2] 0 0
Cycle 1 (28 Days)
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Randomization to date of death from any cause (Up to 83 months)
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)
Secondary outcome [5] 0 0
Percentage of Participants Achieving an Objective Response (Response Rate)
Timepoint [5] 0 0
Randomization to measured progressive disease (Up to 36 Weeks)
Secondary outcome [6] 0 0
Duration of Tumor Response (DoR)
Timepoint [6] 0 0
Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)
Secondary outcome [7] 0 0
Time to Treatment Failure (TTF)
Timepoint [7] 0 0
Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause (Up to 75 Weeks)
Secondary outcome [8] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score
Timepoint [8] 0 0
Baseline, Day 1 Cycle 4
Secondary outcome [9] 0 0
Time to Worsening (TTW) of Symptoms (FACT-Hep)
Timepoint [9] 0 0
Baseline to the worsening of symptoms (up to 567 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
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. - Nedlands
Recruitment hospital [2] 0 0
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. - Greenslopes
Recruitment hospital [3] 0 0
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 - Heidelberg
Recruitment hospital [4] 0 0
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. - St. Leonards
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
2065 - St. Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
France
State/province [10] 0 0
Brest
Country [11] 0 0
France
State/province [11] 0 0
Caen
Country [12] 0 0
France
State/province [12] 0 0
Clichy
Country [13] 0 0
France
State/province [13] 0 0
Creteil
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
France
State/province [15] 0 0
Lyon
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Montpellier
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Pessac
Country [20] 0 0
France
State/province [20] 0 0
Saint Etienne
Country [21] 0 0
France
State/province [21] 0 0
Saint Herblain
Country [22] 0 0
France
State/province [22] 0 0
Strasbourg
Country [23] 0 0
France
State/province [23] 0 0
Vandoeuvre Les Nancy
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Erlangen
Country [26] 0 0
Germany
State/province [26] 0 0
Göttingen
Country [27] 0 0
Germany
State/province [27] 0 0
Köln
Country [28] 0 0
Germany
State/province [28] 0 0
Mainz
Country [29] 0 0
Germany
State/province [29] 0 0
Münster
Country [30] 0 0
Italy
State/province [30] 0 0
Bari
Country [31] 0 0
Italy
State/province [31] 0 0
Rome
Country [32] 0 0
Italy
State/province [32] 0 0
Rozzano
Country [33] 0 0
New Zealand
State/province [33] 0 0
Auckland
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.