| General information |
| Database: | DB00995 |
| Objective: | Thisphase 2 study evaluated trebananib (AMG 386), an investigational peptideFc fusion protein that neutralises the interaction between angiopoietins1/2 and the Tie2 receptor, plus FOLFIRI as secondline treatment for patients with metastatic colorectal cancer. |
| Authors: | Peeters M, et al |
| Title: | A randomised, doubleblind, placebocontrolledphase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma. |
| Journal: | Br J Cancer. |
| Year: | 2013 |
| PMID: | 23361051 |
| Trial Design |
| Clinical Trial Id: | NCT00752570 |
| Agent: | trebananib
|
| Target: | Angiopoietin2, Angiopoietin1
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | trebananib (AMG 386) + FOLFIRI |
| Study Type: | A randomised, doubleblind, placebocontrolledphase II study |
| Key Patients Feature: | Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatinbased chemotherapy regimen for metastatic disease |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | trebananib (AMG 386) in combination with FOLFIRI versus placebo in combination with FOLFIRI |
| Treatment Info: | All patients received FOLFIRI and were randomised 2:1 to also receive intravenous trebananib 10 mg kg(1) once weekly (QW) (Arm A) or placebo QW (Arm B). |
| Primary End Point: | investigatorassessed progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 144 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 14% and 0% in Arms A and B |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.811.86; P=0.33) |
| Median OS A vs. C: | 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.531.54; P=0.70) |
| Adverse Event(agent arm): | The incidence of AEs identified as being of specific interest before the study was initiated (including arterial and venous thromboembolic events, hypertension, and perforations) was generally similar across both treatment arms (Table 4); however, some AEs warrant special mention. There was one gastrointestinal perforation (grade 3 abdominal abscess) and one grade 5 pulmonary oedema (both in Arm A). Additionally, one patient in Arm A had grade 5 acute myocardial infarction, one patient had grade 4 pulmonary embolism, and one patient had grade 4 cerebral venous thrombosis. In Arm B, one patient had grade 4 arterial thrombosis and two patients had grade 4 pulmonary embolism. |
| Conclusions: | Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities they were manageable and consistent with those known for FOLFIRI and trebananib. |