| General information |
| Database: | DB00716 |
| Objective: | They evaluated AMG 386, an investigational peptibody that neutralizes the interaction between angiopoietins1 and 2 and the Tie2 receptor, combined with cisplatin/capecitabine (CX) as firstline treatment for metastatic gastrooesophageal cancer. |
| Authors: | Eatock MM, et al |
| Title: | Phase II randomized, doubleblind, placebocontrolled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastrooesophageal cancer. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 23108953 |
| Trial Design |
| Clinical Trial Id: | NCT00583674 |
| Agent: | trebananib
|
| Target: | Angiopoietin2, Angiopoietin1
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the lower oesophagus, oesophagealjunction or stomach |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | AMG 386 (trebananib) + cisplatin and capecitabine |
| Study Type: | Phase II randomized, doubleblind, placebocontrolled study |
| Key Patients Feature: | Eligible patients (more than and equal to 18 years) had metastatic histologically or cytologicallyconfirmed gastric, gastrooesophageal junction, or distal oesophagealadenocarcinoma; measurable or nonmeasurable disease per ResponseEvaluation Criteria in Solid Tumours (RECIST) version 1.0 [27]; EasternCooperative Oncology Group (ECOG) performance status less than and equal to 1; were able toswallow oral medications; and had adequate haematologic, coagulation, hepatic, cardiac, and renal function |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | AMG 386 10 mg/kg QW (Arm A) or 3 mg/kg QW (Arm B), or placebo QW (Arm C) |
| Treatment Info: | Patients with metastatic gastric, gastrooesophageal junction, or distal oesophageal adenocarcinoma were randomized 1:1:1 to CX (cisplatin 80 mg/m(2) IV Q3W; capecitabine 1000 mg/m(2) P.O. BID for 14 days Q3W) plus intravenous AMG 386 10 mg/kg QW (Arm A) or 3 mg/kg QW (Arm B), or placebo QW (Arm C). |
| Primary End Point: | estimated progression free survival (PFS) |
| Secondary End Point: | ORR per RECIST, duration of response (DOR), OS, time to response, time to progression (TTP), incidence of adverse events (AEs) and antiAMG386 antibodies, and assessment of AMG 386 pharmacokinetics. Evaluation of angiogenic biomarkers was an exploratory end point. |
| Patients Number: | 171 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Objective response rates were 27% (Arm A), 43% (Arm B), and 35% (Arm C). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Arms A, B, and C was 4.2, 4.9, and 5.2 months, respectively (hazard ratio for Arms A+B combined versus Arm C, 0.98; 95% CI 0.67-1.43; P= 0.92). |
| Median OS A vs. C: | 9.1, 9.4, and 12.8 months for Arms A, B, and C, respectively. |
| Adverse Event(agent arm): | The incidence of AEs (any grade) was similar across the three treatment arms. AEs occurring more frequently in the AMG 386 arms included fatigue, decreased appetite, diarrhoea, constipation, abdominal pain, and peripheral oedema, which was primarily of grade <3. There was no notable difference in the patient incidence of grade 3 and grade 4 AEs between treatment arms. however, more serious AEs occurred in the AMG 386 arms relative to placebo (Arms A/B/C, 73/60/47%), including vomiting (5/21/9%), nausea (5/12/2%), anaemia (11/10/8%), and abdominal pain (11/3/2%), and more patients receiving AMG 386 than placebo discontinued all treatment (i.e. AMG 386/placebo, capecitabine, and cisplatin) because of AEs (30/26/9%). |
| Conclusions: | In this study, PFS and ORR they were estimated to be similar with AMG 386 plus CX and placebo plus CX treatment. Compared with placebo, toxicity of AMG 386 plus CX was greater but manageable. |