A Study of Ramucirumab (LY3009806) and best supportive care inParticipants with Hepatic Cancer
- Conditions
- Hepatocellular CarcinomaMedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005068-13-IT
- Lead Sponsor
- ELI LILLY & COMPANY, LILLY CORPORATE CENTER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 323
[1] The patient has a diagnosis of HCC based on either:
a. histopathologic or cytologic findings
b. in the absence of histologic confirmation, a diagnosis of cirrhosis and HCC with classical imaging characteristics (that is, at least a 3-phase liver protocol CT or MRI and a lesion that demonstrates arterial hyperenhancement and washes out in the venous phase).
[2] The patient received sorafenib treatment for at least 14 days and discontinued sorafenib treatment =14 days prior to randomization.
[3] The patient experienced radiographically confirmed disease progression during or after discontinuation of sorafenib therapy or discontinued sorafenib treatment because of intolerance despite appropriate sorafenib management and supportive care.
[4] The patient received sorafenib as the only systemic therapeutic intervention for advanced HCC.
[5] The patient has =1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (Eisenhauer et al. 2009) that has not been previously treated with locoregional therapy.
[6] The patient is ¿18 years of age or of an age acceptable according to local regulations, whichever is older.
[7] The patient has a Child-Pugh score of <7 (Child-Pugh Class A only).
[8] The patient has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy.
[9] The patient has a baseline AFP = 400 ng/mL, as determined by local laboratory testing.
Inclusion criteria for the Open-label Cohort are:
Protocol Inclusion Criteria [2], [3], and [4] do not apply to the Open-Label Cohort. All other inclusion criteria apply to the Open-Label Cohort.
The following additional Inclusion Criterion apply to the Open-Label Cohort:
-The patient received 1 prior systemic therapy regimen, excluding prior sorafenib, for the treatment of HCC.
-The patient discontinued from prior systemic therapy 14 days prior to enrollment.
-The patient experienced radiographically confirmed disease progression during or after discontinuation of prior systemic therapy or discontinued prior systemic treatment because of intolerance, despite appropriate management and supportive care.
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 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 153
17] The patient has fibrolamellar carcinoma or mixed hepatocellular
cholangiocarcinoma.
[18] The patient had a previous or has concurrent malignancy. Patients
with carcinoma in situ of any origin and patients with prior malignancies
who are in remission and whose likelihood of recurrence is very low, as
judged by the investigator, may be eligible for this study in consultation
with and approval by the Lilly CRP.
[19] The patient has previously documented brain metastases,
leptomeningeal disease, or uncontrolled spinal cord compression.
[20] The patient has a history of or current hepatic encephalopathy
(any grade) or clinically meaningful ascites. Clinically meaningful
ascites is defined as CTCAE Grade >1 ascites resulting from cirrhosis.
Patients who have been on a stable medical regimen (for =3 months) to
manage ascites are eligible if they show no evidence of ascites on
clinical exam that would require further intervention.
[21] The patient has ongoing or recent (=6 months prior to
randomization) hepatorenal syndrome.
[22] The patient had a prior liver transplant.
[23] The patient received any previous systemic therapy with VEGF
inhibitors or VEGF-Receptor inhibitors (including investigational agents)
other than sorafenib for treatment of HCC.
[24] The patient received any hepatic locoregional therapy (including
radiation, surgery, hepatic arterial embolization, chemoembolization,
radiofrequency ablation, cryoablation, or percutaneous ethanol
injection) following sorafenib or within 28 days prior to randomization.
Use of locoregional therapy prior to sorafenib is allowed.
[25] The patient received radiation to any nonhepatic (for example,
bone) site within 14 days prior to randomization. Prior radiation to
>25% total bone marrow is not allowed.
Protocol Exclusion Criteria [23] and [24] do not apply to the Open-Label Cohort. All other exclusion criteria apply to the Open-Label Cohort.
The following additional Exclusion Criterion applies to the Open-Label Cohort:
-The patient received any hepatic locoregional therapy (including radiation, surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, cryoablation, or percutaneous ethanol
injection) following prior systemic therapy or within 28 days prior to randomization. Use of locoregional therapy prior to completion of systemic therapy is allowed.
The following additional Exclusion Criteria apply to patients who received prior immunotherapy (for example, inhibitors of programmed death 1, programmed death ligand 1, and/or cytotoxic T lymphocyte
antigen 4):
-The patient is experiencing, or has experienced, any of the following:
a. any clinically significant Grade 3 immune-related adverse event (irAE)
b. any grade neurologic or ocular irAE
c. any grade immune-related pneumonitis, cardiomyopathy, or hepatitis
-At the time of study enrollment, the patient requires steroids or other immunosuppressive agents (such as anti-thymocyte globulin [ATG] or cyclosporine).
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