| General information |
| Database: | DB00464 |
| Objective: | They aimed to assess the safety, efficacy, biomarkers, and pharmacokinetics of rilotumumab combined with epirubicin, cisplatin, and capecitabine (ECX) in patients with advanced gastric or oesophagogastric junction cancer. |
| Authors: | Iveson T, et al |
| Title: | Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as firstline treatment for gastric or oesophagogastric junction adenocarcinoma: an openlabel, dose deescalationphase 1b study and a doubleblind, randomisedphase 2 study. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24965569 |
| Trial Design |
| Clinical Trial Id: | NCT00719550 |
| Agent: | rilotumumab
|
| Target: | Hepatocyte growth factor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Rilotumumab + epirubicin, cisplatin, and capecitabine |
| Study Type: | an openlabel, dose deescalationphase Ib study and a doubleblind, randomisedphase II study |
| Key Patients Feature: | Eligible patients (more than and equal to 18 years) had pathologicallyconfirmed, unresectable locally advanced or metastaticgastric or oesophagogastric junction adenocarcinoma.Tumours of the distal oesophagus within 5 cm of theoesophagogastric junction were allowed. Measurable andnonmeasurable disease were also allowed. Otherinclusion criteria included an Eastern CooperativeOncology Group (ECOG) performance status of 0 or 1; lifeexpectancy of at least 3 months; adequate organ function;haemoglobin concentration of at least 90 g/L; absoluteneutrophil count of at least 1.5 ¡Á 10 cells per L; plateletcount of at least 100 ¡Á 10 platelets per L (without transfusion <14 days before enrolment or randomisation);creatinine clearance of at least 60 mL/min (calculated ormeasured); aspartate aminotransferase (AST) and alanineaminotransferase (ALT) concentrations of less than orequal to 2.5 ¡Á upper limit of normal (ULN), or AST andALT of 5 ¡Á ULN or less in the presence of liver metastasis;total bilirubin 1.5 ¡Á ULN or less; and partial thromboplastintime 1.5 ¡Á ULN or less and international normalisationratio less than or equal to the ULN. |
| Biomarker: | METpositive |
| Biomark Analysis: | NA |
| Control Group Info: | rilotumumab or placebo |
| Treatment Info: | Phase 1b was an openlabel, dose deescalation study to identify a safe dose of rilotumumab (initial dose 15 mg/kg intravenously on day 1) plus ECX (epirubicin 50 mg/m(2) intravenously on day 1, cisplatin 60 mg/m(2) intravenously on day 1, capecitabine 625 mg/m(2) twice a day orally on days 121, respectively), administered every 3 weeks.phase 2 was a doubleblind study that randomly assigned patients (1:1:1) using an interactive voice response system to receive rilotumumab 15 mg/kg, rilotumumab 7.5 mg/kg, or placebo, plus ECX (doses as above), stratified by ECOG performance status and disease extent. |
| Primary End Point: | the incidence of doselimiting toxicities.the phase 2 primary endpoint was progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 9 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Rilotumumab 15 mg/kg plus ECX group (n=40), Complete response 0, Partial response 31%, Stable disease 44%, Progressive disease 14%;in Rilotumumab 7.5 mg/kg plus ECX group(n=42), Complete response 3%, Partial response 45%, Stable disease 38%, Progressive disease 10%;in rilotumumab plus ECX groups group(n=82), Complete response 1%, Partial response 38%, Stable disease 41%, Progressive disease 12%;in Placebo plus ECX group(n=39), Complete response 0, Partial response 21%, Stable disease 55%, Progressive disease 13%; |
| Disease Control Rate: | 75% in the rilotumumab 15 mg/kg group, 85% in the rilotumumab 7.5 mg/kg group, 80% in both rilotumumab groups combined, and 76% in the placebo group. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.1 months (95% CI 2.9-7.0) in the rilotumumab 15 mg/kg group, 6.8 months (4.5-7.5) in the rilotumumab 7.5 mg/kg group, 5.7 months (4.5-7.0) in both rilotumumab groups combined, and 4.2 months (2.9-4.9) in the placebo group. |
| Median OS A vs. C: | 9.7 (7.7-13.3) months in the rilotumumab 15 mg/kg group, 11.1 (9.2-13.2) months in the rilotumumab 7.5 mg/kg group, 10.6 (9.2-12.5) months in both rilotumumab groups combined, and 8.9 (5.5-11.2) months in the placebo group. |
| Adverse Event(agent arm): | Any grade adverse events more common in the combined rilotumumab group than in the placebo group included haematological adverse events (neutropenia in 44 [54%] of 81 patients vs 13 [33%] of 39 patients; anaemia in 32 [40%] vs 11 [28%]; and thrombocytopenia in nine [11%] vs none), peripheral oedema (22 [27%] vs three [8%]), and venous thromboembolism (16 [20%] vs five [13%]). Grade 3-4 adverse events more common with rilotumumab included neutropenia (36 [44%] vs 11 [28%]) and venous thromboembolism (16 [20%] vs four [10%]). Serious adverse events were balanced between groups except for anaemia, which occurred more frequently in the combined rilotumumab group (ten [12%] vs none). |
| Conclusions: | Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX. Aphase 3 study of the combination in METpositive gastric and oesophagogastric junction cancer is in progress. |