CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00038
Objective:Biologically targeted therapies have been postulated as a viable strategy to improve outcomes for women with ovarian cancer. They assessed the safety, tolerance, pharmacokinetics, relevant circulating and imagederived biomarkers, and clinical activity of combination aflibercept and docetaxel in this population.
Authors:Coleman RL, et al
Title:Phase 12 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer.
Journal:Lancet Oncol.
Year:2011
PMID:21992853
Trial Design
Clinical Trial Id:NCT00436501
Agent:aflibercept
Target:VEGFA, vascular endothelial growth factor B, PIGF
Cancer Type:ovarian cancer
Cancer Subtype:epithelial ovarian, primary peritoneal, or fallopian tube carcinoma
Therapy Type:com
Therapeutic Combination Type:2
Therapeutic Combination Content:docetaxel + aflibercept
Study Type:a phase III study
Key Patients Feature:eligible patients had measurable, recurrent or persistent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with a maximum of two prior chemotherapy regimens
Biomarker:NA
Biomark Analysis:NA
Control Group Info:single arm
Treatment Info:phase 1: Aflibercept was administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose for the phase 2 study. Pharmacokinetics were assessed and dynamic imaging was done during a leadinphase with singleagent aflibercept (cycle 0) and during combination therapy with intravenous docetaxel (75 mg/m(2)).phase 2: patients were enrolled in a twostage design and given aflibercept 6 mg/kg intravenously and docetaxel 75 mg/m(2) intravenously, every 3 weeks.
Primary End Point:objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.0.
Secondary End Point:NA
Patients Number:46
Trial Results
DLT_MTD:RP2D of aflibercept and docetaxel were found to be 6 mg/kg and 75 mg/m(2).No doselimiting toxicities were noted.
Objective Response Rate:(46)33 were platinum resistant (15 refractory) and 13 were platinum sensitive; The confirmed ORR was 54% (25 of 46; 11 patients had a complete response and 14 had a partial response).
Disease Control Rate:NA
Median Time to Progression:NA
Median PFS A vs. C:NA
Median OS A vs. C:NA
Adverse Event(agent arm):Grade 34 toxicities observed in more than two patients (5%) were: neutropenia in 37 patients (80%); leucopenia in 25 patients (54%); fatigue in 23 patients (50%); dyspnoea in ten patients (22%); and stomatitis in three patients (7%). Adverse events specifically associated with aflibercept were grade 12 hypertension in five patients (11%), and grade 2 proteinuria in one patient (2%).
Conclusions:Combination aflibercept plus docetaxel can be safely administered at the dose and schedule reported here, and is associated with substantial antitumour activity. These findings suggest that further clinical development of this combination in ovarian cancer is warranted.