Iveson 2014.
Methods | International RCT (43 centers), Phase II | |
Participants |
Number of participants: 121 (February 2009 to November 2010) Number randomized: Experimental group A (ECX (epirubicin, cisplatin, and capecitabine) + rilotumumab 7.5 mg/kg): 42 Experimental group B (ECX + rilotumumab 15 mg/kg): 40 Control group (ECX + placebo): 39 Number evaluated: Experimental group A: 42, age (median and range): 62 (27 ‐ 78) years Experimental group B(ECX + rilotumumab 15 mg/kg): 40, age (median and range): 59.5 (28 ‐ 76) years Control group: 39, age (median and range): 60 (39 ‐ 79) years Diagnosis: patients with unresectable locally‐advanced or metastatic gastric or esophagogastric junction adenocarcinoma Inclusion: eligible patients should: be > 18 years; have pathologically‐confirmed, unresectable locally‐advanced or metastatic gastric or esophagogastric junction adenocarcinoma (tumors of the distal esophagus within 5 cm of the esophagogastric junction were allowed); measurable and non‐measurable disease; ECOG performance status of 0 or 1; life expectancy of at least 3 months; adequate organ function; hemoglobin concentration of at least 90 g/L; absolute neutrophil count of at least 1.5*10⁹ cells per L; platelet count of at least 100*10⁹ platelets per L (without transfusion < 14 days before enrolment or randomization); creatinine clearance of at least 60 mL/min (calculated or measured); AST and ALT concentrations of ≤ 2·5 × ULN, or AST and ALT of 5 × ULN or less in the presence of liver metastasis; total bilirubin 1·5 × ULN or less; and partial thromboplastin time 1·5 × ULN or less and international normalization ratio ≤ the ULN |
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Interventions |
Experimental group A : intravenous infusion of rilotumumab 7.5 mg/kg before administration of ECX + ECX (epirubicin 50 mg/m² administered intravenously on day 1 every 3 weeks; cisplatin 60 mg/m² administered intravenously on day 1 every 3 weeks, and capecitabine 625 mg/m² taken twice a day orally on days 1 – 21 every 3 weeks) Experimental group B : intravenous infusion of rilotumumab 15 mg/kg before administration of ECX + ECX (epirubicin 50 mg/m² administered intravenously on day 1 every 3 weeks; cisplatin 60 mg/m² administered intravenously on day 1 every 3 weeks, and capecitabine 625 mg/m² taken twice a day orally on days 1 – 21 every 3 weeks) Control group: intravenous infusion of placebo before administration of ECX + ECX (epirubicin 50 mg/m² administered intravenously on day 1 every 3 weeks; cisplatin 60 mg/m² administered intravenously on day 1 every 3 weeks, and capecitabine 625 mg/m² taken twice a day orally on days 1 – 21 every 3 weeks) Treatment continued for up to 10 cycles or until disease progression, unacceptable toxicity, or withdrawal of informed consent |
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Outcomes |
Duration of follow‐up (median): 21.7 months (IQR 20.5 ‐ 23.5) PFS, OS, overall response, adverse events |
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Notes | Sponsor: Amgen The sponsor was involved in the study design, data collection, data analysis, results interpretation, and manuscript preparation |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | "The randomisation list was generated using permuted blocks with a block size of six and prepared by an individual independent of the study team" |
Allocation concealment (selection bias) | Low risk | "Treatment allocation was assigned using an interactive voice response system" |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Patients, investigators, and the study team were masked to treatment allocation, which was straightforward because rilotumumab is a colourless liquid." |
Blinding of outcome assessment (detection bias) OS, Serious adverse events | Low risk | These outcomes were unlikely to be affected by the blindness status of assessors |
Blinding of outcome assessment (detection bias) PFS, Response, quality of life & adverse events | Low risk | "Patients, investigators, and the study team were masked to treatment allocation, which was straightforward because rilotumumab is a colourless liquid." |
Incomplete outcome data (attrition bias) All outcomes | Low risk | 121 randomized participants were included in analysis (100%) |
Selective reporting (reporting bias) | Low risk | Prior protocol was available |
Other bias | Low risk | No obvious potential source of bias |