Hepatocellular Carcinoma (HCC)
Conditions
Interventions
Product Name: LY2181308 Sodium
Product Code: LY2181308
Pharmaceutical Form: Solution for infusion
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients may be included in the study only if they meet all of the following criteria: 1. Patients previously diagnosed with HCC. Primary HCC diagnoses may be histopathological, cytological, or clinically confirmed. Patients with only a clinical diagnosis of HCC are acceptable, if diagnosis was made following the AASLD-EASL diagnostic consensus. Patients entering the trial after progression from a previous liver cancer therapy do not need to be rebiopsied. Progression, per modified RECIST criteria (Attachment JACS.7), should be documented before entering the trial. 2. HCC in a BCLC (refer to Protocol Attachment JACS.5) stage at the time of entering the trial of either intermediate (B) or advanced (C) groups. Early stage tumors (A) can be enrolled if any of the potentially curative standard therapies for these cases [i.e. liver transplantation, surgical resection, transcatheter arterial chemoembolization (TACE) or percutaneous embolization] is excluded due to tumor localization, patient’s underlying conditions or because of tumor recurrence. 3. Patients must have discontinued and recovered from the acute effects of all previous therapies for their cancer (e.g., sorafenib, chemotherapy, radiotherapy, or other investigational therapy) for at least 2 weeks prior to enrollment (3 weeks in the case of cytotoxics). 4. For Phase 2 only: Measurable disease by modified RECIST criteria for HCC (See Attachment JACS.7). Patient should have at least one lesion which has not been previously treated locally with percutaneous or transcatheter arterial chemoembolization (TACE). 5. Liver function determined in Child-Pugh class A or B of 7 points (refer to Protocol Attachment JACS.6). 6. Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance status scale. (refer to Protocol Attachment JACS.3) 7. The following laboratory results: • Hematology Neutrophils =1.5 x 10E9/L Hemoglobin =9g/dL Platelets =100 x 10E9/L • Hepatic Any bilirubin and albumin values that are within the acceptable range per the Child Pugh Score will be eligible for participation (See inclusion criteria #5) Alanine Aminotransferase (ALT) =10 times ULN Aspartate Aminotransferase (AST) =10 times ULN Alkaline Phosphatase (AP) =5 times ULN Coagulation: Activated partial thromboplastin time (aPTT) =1.5 times ULN and International Normalized Ratio (INR) of prothrombin time =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria: 1. HCC that could be treated with potentially curative or effective palliative therapies (e.g., surgical resection, liver transplant, percutaneous ablation, transcatheter arterial embolization (TACE), sorafenib and/or other proven effective therapies). 2. Patients who have received a liver transplant. 3. Second primary malignancy except in situ carcinoma of the cervix or adequately treated non-melanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence; prior low grade [Gleason score =6] localized prostate cancer is allowed. 4. Previous systemic antisense oligonucleotide treatment. 5. Hepatic encephalopathy of any degree or requirement for chronic treatment to control (it is acceptable to enroll patients with one or more previous events that were short-lived which remained without treatment). 6. Concurrent chronic infection with Human Immunodeficiency Virus (HIV). 7. Patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. 8. Patients with active alcohol abuse or illicit drug use. 9. Patients with serious concomitant systemic disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient’s ability to complete the study. 10. Female patients who are pregnant or breast-feeding. 11. Symptomatic or proven central nervous system (CNS) neoplasm. 12. Concomitant anticancer therapy or anticoagulant therapy (with the exception of the use of heparinized saline to maintain patency of central venous catheters). 13. Patients taking acetylsalicylic acid (ASA, aspirin) and NSAIDS less than one week prior to treatment. 14. Patients taking G-CSF (Growth-Colony Stimulating Factor) less than 24 hours prior to the start of therapy. 15. Patients who require palliative radiotherapy at the time of study entry. 16. Patients with more than 2 previous systemic chemotherapy treatments (excluding tamoxifen).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective : Phase 1b: To determine the recommended dose for the Phase 2 portion of this trial for patients with advanced hepatocellular cancer (HCC) with no other standard curative or palliative therapeutic option. Phase 2: To estimate the time to progression (TTP) for patients with advanced HCC who have received LY2181308. ;Secondary Objective: Secondary objectives: -To estimate overall survival time and progression-free survival. -To evaluate the safety of LY2181308 in the HCC patient population. -To evaluate response rate based on RECIST criteria modified for HCC. -To evaluate LY2181308 PK in the HCC patient population. -To evaluate the effect of LY2181308 on the number of circulating tumor cells and survivin expression in these cells. ;Primary end point(s): In this study, the primary objective is to estimate TTP median and its 90% confidence intervals (CI). Time-to-progression is defined as the time from the date of first treatment dose to the first date of progressive disease. For patients not known to have disease progression as of the data cut-off date, the TTP date will be censored as the last contact date or at the date of death. The analysis will be performed using the Kaplan-Meier method (Kaplan and Meier 1958). For this single-arm trial, hypothesis tests comparing the time-to-progression median from this study with historical values are not planned. | — |
Countries
Germany, Spain
Outcome results
None listed