E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019829 |
E.1.2 | Term | Hepatocellular carcinoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to characterize and compare both the time-toprogression
(TTP) distributions and the effect on transforming growth factor beta (TGF--associated
serum biomarkers (for example, TGF-, alpha-fetoprotein (AFP), E-cadherin) of 2 doses of LY2157299
in patients with hepatocellular carcinoma (HCC). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety of LY2157299 in HCC patients
- To evaluate the population pharmacokinetics (PK) of LY2157299
- To determine E-cadherin, pSMAD, beta-integrin presence in the original diagnostic tumor tissue and optional
posttreatment tumor tissue and the correlation of this with both clinical efficacy endpoints and biomarker
response.
- To recommend which dose to use in future trials recruiting HCC patients
- To characterize other time-to-event distributions, such as progression-free survival, overall survival
- To estimate antitumor efficacy using response rate
- To assess patient-reported outcome (PRO) measures of disease-specific symptoms and healthrelated quality of
life.
- To explore the utility of exploratory imaging techniques to assess treatment effect with LY2157299 when
possible
- Explore fibrosis-related biomarkers, such as Fibrotest |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Have histological evidence of a diagnosis of HCC not amenable to curative surgery
[2] Child-Pugh Stage A
[3] Serum AFP ≥1.5 upper limit of normal (ULN)
[4] Have the presence of measurable disease as defined by the RECIST 1.1 (Eisenhauer et al. 2009; . 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.
[5] Age >18 years
[6] Have given written informed consent prior to any study-specific procedures
[7] Have adequate organ function including:
- Hematologic: absolute neutrophil count (ANC) >1.5 x 109/L, platelets >75 x 109/L, and hemoglobin >8 g/dL
- Hepatic: bilirubin ≤2.5 times ULN); alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) <5ULN. Prothrombin time international normalized ratio, <2.3; or
prothrombin time, <6 seconds above control).
- Renal: Serum creatinine <1.5 times ULN or calculated creatinine clearance >45 mL/min
[8] Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale
[9] Have either:
- received sorafenib and have progressed or were intolerant to sorafenib, or
- are ineligible for sorafenib treatment (at the investigator’s discretion) |
|
E.4 | Principal 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, or concurrently enrolled in any
other type of medical research judged not to be scientifically or medically compatible with this study
[16] Known HCC with fibro-lamellar or mixed histology
[17] Presence of clinically relevant ascites
[18] History of liver transplant
[19] Have received >1 line of systemic treatment
[20] Have moderate or severe cardiac disease: (see Section 8.2)
[21] Have serious preexisting medical conditions that, in the opinion of the investigator, cannot be
adequately controlled with appropriate therapy or would preclude participation in this study
[22] Females who are pregnant or lactating.
[23] Have a history of any other cancer (except nonmelanoma 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
[24] Have active infection that would interfere with the study objectives or influence study compliance |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
|
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |