An Open Label Single Arm Phase 1b/2 Study with Pharmacokinetic Sampling to Evaluate LY2181308 in Patients with Advanced Hepatocellular Carcinoma - N/A
- Conditions
- Hepatocellular Carcinoma (HCC)
- Registration Number
- EUCTR2006-002893-23-DE
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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 <1.7
Patients on treatment with less than 40 mg/day of furosemide and 100
mg/day of spironolactone for ascites control (or equivalent).
• Renal
Calculated creatinine clearance by Cockcroft-Gault formula =50 mL/min
(refer to Protocol Attachment JACS.8).
8. Female patients of child-bearing potential must have a negative pregnancy
test at the time of enrollment based on a serum pregnancy test. Male and
female patients must agree to use a reliable method of birth control during
and for 3 months following the last dose of study drug.
9. Patient must be reliable, compliant with study procedures, and willing to be
available for all study visits for the duration of the study.
10. Patient must sign an Institutional Review Board approved informed consent
document prior to study procedures being performed.
11. Patient must be at least 18 years of age.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method