Study with Pharmacokinetic Sampling to Evaluate LY2181308 in Patients with Advanced Hepatocellular Carcinoma

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2006-002893-23-ES
• Date of registration: 29/03/2012
• Prospective Registration: No
• Primary sponsor: Lilly S.A.
• Public title: Study with Pharmacokinetic Sampling to Evaluate LY2181308 in Patients with Advanced Hepatocellular Carcinoma
• Scientific title: An Open Label, Single Arm, Phase 1b/2 Study with Pharmacokinetic Sampling to Evaluate LY2181308 in Patients with Advanced Hepatocellular Carcinoma - N/A
• Date of first enrolment: 08/03/2007
• Target sample size: 60
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002893-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany, Spain, United States

Contacts

• Name: Clinical Operations
• Affiliation: Lilly S.A.

• Name: Clinical Operations
• Affiliation: Lilly S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
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. (6) 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
? Hepatic
? Renal
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
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).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced hepatocellular carcinoma (HCC)
MedDRA version: 14.1 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: LY2181308 Sodium
Product Code: LY2181308
Pharmaceutical Form: Solution for infusion
Current Sponsor code: LY2181308
Other descriptive name: Survivina
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

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.

Secondary Objective: To estimate the overall survival (OS) and progression-free survival (PFS).
2.2.2. To evaluate the safety of LY2181308 in the HCC patient population.
2.2.3. To evaluate response rate based on Response Evaluation Criteria in Solid
Tumors (RECIST) modified for HCC.
2.2.4. To evaluate LY2181308 PK in the HCC patient population.
2.2.5. To evaluate the effect of LY2181308 on the number of circulating tumor
cells and survivin expression in these cells.

Main Objective: For Phase 1b: To determine the recommended dose for the Phase 2 portion
of this trial for patients with advanced HCC with no other standard curative
or palliative therapeutic option.
For Phase 2: To estimate the TTP for patients with advanced HCC who
have received LY2181308.

Timepoint(s) of evaluation of this end point: until progression for the disease

Secondary Outcome(s)

Secondary end point(s): ? To characterize overall survival time and progression free survival (PFS).
? To evaluate the objective response rate (ORR) based on the modified RECIST
criteria for HCC (refer to protocol attachment JACS.7). The time-to-event variables will be analyzed using the Kaplan-Meier method. The ORR and the 90% CI will be estimated using unadjusted normal approximation for binomial proportions (z approximation). The influence of prognostic and other baseline factors on efficacy endpoints may be considered.

Timepoint(s) of evaluation of this end point: until progression for the disease

Secondary ID(s)

H8Z-MC-JACS

2006-002893-23-DE

Source(s) of Monetary Support

Lilly S.A.