A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Participants With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Biological: Ramucirumab DP (IMC-1121B)Biological: PlaceboOther: BSC
- Registration Number
- NCT01140347
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
This is a Phase 3 multicenter, randomized study evaluating the safety and efficacy of ramucirumab DP plus BSC as a double-blind, placebo-controlled (placebo plus BSC) comparison.
Approximately 544 participants, at least 18 years of age, with Child-Pugh score \< 7 and diagnosed with hepatocellular carcinoma will be randomized. Participants must have received sorafenib as first-line systemic treatment for hepatocellular carcinoma (HCC), and must have discontinued sorafenib prior to entering the study.
Hypothesis: This sample size will allow differentiation of the expected increase in median overall survival (OS), from 8 months in the placebo arm to 10.67 months in the ramucirumab arm.
Upon registration and completion of screening procedures, eligible participants with HCC who have disease progression during or following first-line therapy with sorafenib, or were intolerant to this agent, will be randomized to receive either ramucirumab DP or placebo.
The treatment regimen will be continued until radiographic or symptomatic progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 565
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo and BSC BSC - Ramucirumab DP and BSC Ramucirumab DP (IMC-1121B) - Ramucirumab DP and BSC BSC - Placebo and BSC Placebo -
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Randomization to death from any cause (up to 37 months) OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.
- Secondary Outcome Measures
Name Time Method Cmax of Ramucirumab, Cycle 4 1 hour following completion of Cycle 4 (14-day cycles) infusion Time to Radiographic Progression (TTP) Randomization to PD (up to 36 months) TTP was defined as the time from randomization to the first radiographically documented PD. PD was defined, using RECIST v1.1 criteria, as ≥20% increase in SOD of target lesions, taking as reference smallest sum on study (including baseline sum if it was the smallest). Sum must show an absolute increase of ≥5 mm. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. Participants without PD were censored at the day of the last adequate tumor assessment. Progression occurred immediately after ≥2 missed tumor assessments and were censored at the day of the last adequate tumor assessment prior to the missing assessments. Participants who began new anticancer therapy were censored at the day of their last adequate tumor assessment prior to start of new anticancer therapy.
Change From Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), and end of treatment (up to 34 months) The FHSI-8 is a self-administered 8-item questionnaire that measures a participant's symptoms in the domains of jaundice, stomach pain/discomfort weight loss, and fatigue. Participants rated each item on a 5-point scale from 0 (not at all) to 4 (very much). Item scores were calculated as outlined in the FACIT manual. FHSI-8 total score was the sum of each item's score with a total score ranging from 0 (highly symptomatic) to 32 (asymptomatic).
Number of Participants With Treatment Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)] Prior to treatment and 1 hour post end of infusion for Cycles 1, 4 and 7 (14-day cycles) Participants were considered positive for anti-ramucirumab antibodies \[anti-drug antibodies (ADA)\] if the post-treatment sample had an increase of at least 4-fold in titer from the pretreatment values. If the pretreatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence of ADA.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] Baseline to the date of first evidence of confirmed CR or PR (up to 37 months) ORR was defined, using RECIST v1.1 criteria, as the percentage of participants who achieved a best overall response of CR or PR. CR was defined as the disappearance of all lesions and any intratumor arterial enhancement in target lesions, the normalization of the tumor marker level and all lymph nodes short axis reduced to \<10 mm. PR was defined as ≥30% decrease in the SOD of target lesions, including the short axes of any target lymph nodes, taking as reference the baseline SOD of target lesions, no new lesions and stable nontarget lesions. Percentage of participants was calculated as: (number of participants with CR or PR / number of participants randomized) \* 100.
Number of Participants With Adverse Events (AEs) and the Number of Participants Who Died Baseline to study completion (up to 37 months) The number of participants with serious AEs (SAEs), other non-serious AEs and participants who died. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Maximum Concentration (Cmax) of Ramucirumab, Cycle 1 1 hour following the completion of Cycle 1 (14-day cycle) infusion Progression-Free Survival (PFS) Randomization to PD (up to 36 months) PFS was defined as time from date of randomization until date of objectively determined progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death from any cause. PD was defined as ≥20% increase in sum of diameters (SOD) of target lesions, taking as reference smallest sum on study (including baseline sum if it was smallest). Sum must show a ≥5 millimeter (mm) increase. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. In primary analysis, participants alive and without PD were censored at day of last adequate tumor assessment; progression or deaths without progression occurring immediately after ≥2 missed tumor assessments, were censored at day of the last adequate tumor assessment prior to missing assessments; participants who began new anticancer therapy were censored at day of the last adequate tumor assessment prior to start of new anticancer therapy.
Change From Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), end of treatment (up to 34 months) The EQ-5D is a self-reported, 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire related to the participant's current health state. Each question was scored using a 3 level scale (no problems, some problems, or extreme problems). EQ-5D health state was defined by combining responses from each of the 5 dimensions into a weighted health-state index score according to the United Kingdom (UK) population based algorithm where 0 = death and 1 = perfect health.
Cmax of Ramucirumab, Cycle 7 1 hour following completion of Cycle 7 (14-day cycles) infusion
Trial Locations
- Locations (1)
ImClone Investigational Site
🇹🇭Hat Yai, Thailand