Hepatocellular Carcinoma MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [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 =65 years) yes F.1.3.1 Number of subjects for this age range 153
Exclusion criteria
Exclusion criteria: [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. Exclusion criteria for the Open-label Cohort are: Protocol Exclusion Criteria [22], [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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare overall survival (OS) for ramucirumab versus placebo in patients with advanced HCC after intolerance or progression on prior sorafenib treatment The primary objective of the open-label, nonrandomized, expansion cohort (Open-label Cohort) is to evaluate the safety profile of ramucirumab in patients with advanced HCC after prior systemic therapy other than prior sorafenib.;Secondary Objective: The secondary objectives of the study are to evaluate: • Progression-free survival (PFS) • Time to radiographic progression (TTP) • Objective response rate (ORR) • Safety profile of ramucirumab • Ramucirumab pharmacokinetics (PK) • Immunogenicity of ramucirumab • Time to deterioration in Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) • Time to deterioration in Eastern Cooperative Oncology Group performance status (ECOG PS) • Other Patient-reported outcome (PRO) measures of disease-specific symptoms and health related quality of life The secondary objectives of the Open-label Cohort are to evaluate: ? overall survival (OS) ? progression-free survival (PFS) ? time to radiographic progression ? objective response rate ? ramucirumab pharmacokinetics ? immunogenicity of ramucirumab ? patient-reported outcome (PRO) measures of disease-specific symptoms and health-related quality of life;Primary end point(s): Compare ramucirumab versus placebo in terms of OS in patients with advanced HCC after intolerance or progression on prior sorafenib. Primary end point of the Open-label Cohort is to evaluate the safety profile of ramucirumab in patients with advanced HCC after prior systemic therapy other than prior sorafenib.;Timepoint(s) of evaluation of this end point: The primary analysis will be performed after approximately 221 deaths have been observed. The primary endpoint for Open-label Cohort will be assessed after all patients enrolled in the Open-Label Cohort have completed at least 3 cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of the study are to evaluate: progression-free survival, time to radiographic progression, objective response rate (ORR), safety profile of ramucirumab, ramucirumab pharmacokinetics, immunogenicity of ramucirumab, time to deterioration in Eastern Cooperative Group performance status (ECOG PS), time to deterioration in Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) and otherpatient-reported outcome measures of disease-specific symptoms and health-related quality of life. The secondary objectives of the Open-label Cohort are to evaluate: overall survival (OS); progression-free survival (PFS); time to radiographic progression; objective response rate; ramucirumab pharmacokinetics; immunogenicity of ramucirumab; patient-reported outcome (PRO) measures of disease-specific symptoms and healthrelated quality of life.;Timepoint(s) of evaluation of this end point: Secondary endpoints will be analyzed at the same time as OS and at the same level of significance. 2 safety interim analyses are planned to be performed when approximately 50 and 150 patients have received 3 cycles of study treatment, died, or discontinued study treatment. Thereafter, safety review will be conducted twice annually, or as requested by the IDMC. Secondary end points for the Open-label Cohort will be assessed after all patients enrolled in the Open-Label Cohort have completed at least 3 cycles of ramucirumab or discontinued for any reason. | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Poland, Spain, Switzerland, Taiwan, United Kingdom
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly and Company
Outcome results
None listed