Clinical trial NCT02331927: PERMAD: Personalized Marker-driven Early Switch to Aflibercept in Patients With Metastatic Colorectal Cancer
Official title: Personalized Marker-driven Early Switch to Aflibercept in Patients With Metastatic Colorectal Cancer (PERMAD-Trial) - a Multicenter, Multinational, Two Part, Phase II Trial
Conditions: Metastatic Colorectal Cancer
Summary: The primary objective of the two phase PERMAD trial is the evaluation of the impact of a personalized marker-driven treatment approach with early detection of progression and modification of treatment on cytokines and angiogenic factors (CAF) and efficacy.
In regard of the two parts, the primary objective of the run-in phase (n=50 patients) with conventional switch of chemotherapy together with the anti-angiogenic agent is the determination of a distinct cytokines and angiogenic factor (CAF) profile during treatment with FOLFOX and bevacizumab, which allows early detection/prediction of progressive disease. The primary objective of the marker-driven randomized part (n=150 patients) with marker-driven switch of antiangiogenic agent and maintenance of chemotherapy is the evaluation of the efficacy of an early marker-driven switch of anti-angiogenic treatment (bevacizumab to aflibercept)
This is a multicentre, multinational, open labeled, prospective, randomized, controlled phase II study designed to assess the clinical utility of an early marker driven change of anti-angiogenic treatment (bevacizumab to aflibercept) maintaining the chemotherapy backbone until definite radiological progression in first line treatment of patients with metastatic colorectal cancer. After completing the run in phase of the study, with at least 30 patients completing their first line treatment (due to progression, secondary resection or toxicity) and being evaluable for CAF analyses, the results will be reviewed by an Independent Data Monitoring Committee (IDMC). Based on that review the decision to continue with, modify or cancel the randomized part will be made.
The primary endpoint of the run-in phase with conventional switch of chemotherapy together with the anti-angiogenic agent is:
• Progression free survival (PFS1) of first line treatment
The primary endpoint of the randomized part with marker-driven switch of antiangiogenic agent and maintenance of chemotherapy is:
• Progression free survival rate at 6 months (PFSR@6) after first cycle after randomization.
Interventions:
description: Early marker-driven switch of antiangiogenic treatment (bevacizumab to aflibercept) maintaining the chemotherapy backbone until definite radiological progression.<br/>compared to a conventional treatment approach of changing chemotherapy and antiangiogenic agent at time of radiologic progression.
name: Aflibercept
type: Biological
Study arms:
design_group_description: Conventional switch of chemotherapy together with the antiangiogenic treatment: Bevacizumab and mFOLFOX6 (continuation of same regimen until progressive disease (PD) according to RECIST v1.1, followed by switch to aflibercept and FOLFIRI after PD).
design_group_title: Randomized Part: Arm A
design_group_type: No Intervention
design_group_description: Early marker-driven switch of anti-angiogenic agent and maintenance of chemotherapy: Bevacizumab and mFOLFOX6 will be administered until change of the CAF-profile and at least stable disease according to RECIST v1.1. Change to Aflibercept and mFOLFOX6 (change of bevacizumab to aflibercept and continuation of mFOLFOX6) until PD according to RECIST v1.1, followed by change to FOLFIRI after PD).
design_group_title: Ramdomized Part: Arm B
design_group_type: Experimental
Sponsor: Universität Ulm
Collaborators: Sanofi
Assign Data Management and Biostatistics GmbH
Drug name mappings:
name: 阿柏西普
lang: CN
name: Aflibercept
lang: EN
name: アフリベルセプト（遺伝子組換え）
lang: JP