The purpose of this study is to gather information about the use of an investigational drug called Ramucirumab in adenocarcinomas of the stomach or gastroesophageal junction.
Placebo-controlled, multicenter Phase 3 study of participants with metastatic gastric cancer \[including adenocarcinomas of the gastroesophageal junction (GEJ)\] and disease progression on standard first-line chemotherapeutic regimens. Participants will be randomized on a 2:1 basis to receive best supportive care plus ramucirumab administered every 2 weeks or best supportive care plus placebo administered every 2 weeks, respectively. Participants will undergo radiographic assessment of disease status every 6 weeks. Participant will be treated until there is evidence of progressive disease, toxicity requiring cessation, withdrawal of consent, or until other withdrawal criteria are met. Approximately 348 participants, with histologically- or cytologically-confirmed, metastatic gastric or GEJ adenocarcinoma, and radiographically measurable disease as defined by the Response Evaluation Criteria in Solid Tumors or evaluable, nonmeasurable disease, will be randomized. Participants will be enrolled from approximately 250 study centers in North America, South America, Central America, Asia, Australia, New Zealand, and Europe.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
355
Administered via intravenous infusion every 2 weeks at a dose of 8 mg/kg
Placebo comparator for ramucirumab 8 mg/kg as intravenous infusion every 2 weeks
BSC as determined appropriate by the investigator(s). BSC may include but are not limited to antiemetic agents, opiate and nonopiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.
Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the date of data cut-off or who were lost to follow-up were censored on the last date the participant was known to be alive
Time frame: Randomization up to 28 months post-randomization
Progression-Free Survival (PFS)
PFS is defined as the time from date of randomization until date of objectively determined progressive disease (PD) or death due to any cause, whichever is first. Participants alive and without PD were censored at the time of last adequate objective tumor assessment (that is, response other than unevaluable).
Time frame: Randomization up to 17 months
Percentage of Participants Who Are Progression-Free at Week 12 (PFS Rate)
The percentage of participants alive and progression-free 12 weeks after randomization. Progression-free survival (PFS) is defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) or death due to any cause whichever comes first. Participants alive and without PD were censored at the time of the last adequate objective tumor assessment.
Time frame: Week 12 post-randomization
Percentage of Participants With Objective Response (Objective Response Rate [ORR])
ORR is equal to the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR). CR and PR were defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR is defined as the disappearance of all target and non-target lesions, no appearance of new lesions and confirmed at the consecutive tumor assessment. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, no appearance of new lesions and confirmed at a subsequent tumor assessment.
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ImClone Investigational Site
Bakersfield, California, United States
ImClone Investigational Site
La Jolla, California, United States
ImClone Investigational Site
Redlands, California, United States
ImClone Investigational Site
Chicago, Illinois, United States
ImClone Investigational Site
New Orleans, Louisiana, United States
ImClone Investigational Site
Boston, Massachusetts, United States
ImClone Investigational Site
Omaha, Nebraska, United States
ImClone Investigational Site
New York, New York, United States
ImClone Investigational Site
West Reading, Pennsylvania, United States
ImClone Investigational Site
Providence, Rhode Island, United States
...and 151 more locations
Time frame: Randomization up to 17 months post-randomization
Duration of Response (DOR)
DOR is the interval from date of initial documented response (complete response \[CR\] or partial response \[PR\]) to first documented date of disease progression (PD) or death as a result of any cause. CR and PR were defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR is defined as the disappearance of all target and non-target lesions, no appearance of new lesions and confirmed at the consecutive tumor assessment. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, no appearance of new lesions and confirmed at a subsequent tumor assessment. Participants who did not relapse or die were censored at the time of the last adequate objective tumor assessment.
Time frame: Randomization up to 17 months post-randomization
Change From Baseline in Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer Questionnaire (EORTC-QLQ-C30)
EORTC QLQ-C30 v3.0 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. Best change from baseline results determined by Least Square (LS) mean estimated with randomization stratification factors and baseline value as continuous covariate.
Time frame: Baseline up to Cycle 10 (18 weeks [1 cycle=2 weeks])
Number of Participants With Adverse Events
Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and all other NSAEs is located in the Reported Adverse Event module.
Time frame: Randomization up to 18 months
Maximum Concentration (Cmax) of IMC-1121B
Cmax was not analyzed as only pre-dose samples were collected.
Time frame: 6 weeks post-randomization
Number of Participants Who Developed Antibodies Against IMC-1121B
The number of participants who developed treatment emergent antibody responses to IMC-1121B after baseline.
Time frame: Baseline, 12 Weeks