A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 3 Study of Weekly Paclitaxel With or Without Ramucirumab (IMC-1121B) in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine
Overview
- Phase
- Phase 3
- Intervention
- Ramucirumab
- Conditions
- Gastroesophageal Junction Adenocarcinoma
- Sponsor
- Eli Lilly and Company
- Enrollment
- 440
- Locations
- 32
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy of the study drug known as ramucirumab in participants with gastric and gastroesophageal cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have an Eastern Cooperative Oncology Group Performance Status (ECOGPS) of 0 or 1 at study entry.
- •Have a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma.
- •Have metastatic disease or locally advanced, unresectable disease.
- •Have at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.
- •Have experienced documented objective radiographic or symptomatic disease progression during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet for unresectable or metastatic disease.
- •Have adequate organ function.
- •Have urinary protein ≤1+ on dipstick or routine urinalysis.
Exclusion Criteria
- •Have undergone major surgery within 28 days prior to randomization.
- •Have received any first-line chemotherapy other than platinum and fluoropyrimidine with or without anthracycline for advanced gastric or GEJ adenocarcinoma.
- •Have received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor (VEGF) or the VEGF receptor signaling pathways.
- •Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to randomization.
- •Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry.
- •Have a history of GI perforation and/or fistulae within 6 months prior to randomization.
- •Have experienced any arterial thromboembolic event within 6 months prior to randomization.
- •Have uncontrolled arterial hypertension (systolic blood pressure ≥160 millimeters of mercury \[mmHg\] or diastolic blood pressure ≥100 mmHg) despite standard medical management.
- •Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to randomization.
- •Have a serious illness or medical condition(s).
Arms & Interventions
8 milligram/kilogram (mg/kg) Ramucirumab + 80 mg/square meter (mg/m²) Paclitaxel
8 mg/kg ramucirumab was administered as an intravenous infusion (IV) on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Intervention: Ramucirumab
8 milligram/kilogram (mg/kg) Ramucirumab + 80 mg/square meter (mg/m²) Paclitaxel
8 mg/kg ramucirumab was administered as an intravenous infusion (IV) on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Intervention: Paclitaxel
Placebo + 80 mg/m² Paclitaxel
Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Intervention: Paclitaxel
Placebo + 80 mg/m² Paclitaxel
Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Randomization to the Date of the First Radiographically Documented Progressive Disease or Death from Any Cause (Up To 30 Months)
PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Overall Survival (OS)
Time Frame: Randomization to Date of Death from Any Cause (Up To 37 Months)
OS defined as the time from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.
Secondary Outcomes
- Time to Progression (TTP)(Randomization to the Date of the First Radiographically Documented Progressive Disease (Up To 30 Months))
- Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])(Randomization to Objective Disease Progression (Up To 30 Months))
- Best Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months))
- Duration of Objective Response (DoR)(Date of Objective Response to the Date of the First Radiographically Documented Progressive Disease or Death Due to Any Cause (Up To 24 Months))
- Worst Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months))
- Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score(Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months))
- Change From Baseline in Participant-Reported EQ-5D-3L Visual Analog Scale (VAS) Score(Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months))