Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature

Alexander Stein, Gabriel Glockzin, Andreas Wienke, Dirk Arnold, Thomas Edelmann, Bert Hildebrandt, Stephan Hollerbach, Gerald Illerhaus, Alfred Königsrainer, Michael Richter, Hans J Schlitt, Hans-Joachim Schmoll, Alexander Stein, Gabriel Glockzin, Andreas Wienke, Dirk Arnold, Thomas Edelmann, Bert Hildebrandt, Stephan Hollerbach, Gerald Illerhaus, Alfred Königsrainer, Michael Richter, Hans J Schlitt, Hans-Joachim Schmoll

Abstract

Background: More than half of patients with colorectal cancer will develop metastatic disease either evident at the time of initial diagnosis or during their course of disease. Besides multidisciplinary management further treatment intensification is warranted to improve the still limited prognosis.

Methods/design: In these two multi-centre, randomized phase II trials, conducted in Germany, 380 patients with R0-resectable colorectal liver metastases (PERIMAX) and with unresectable, metastatic colorectal cancer (CHARTA) will be recruited. Patients previously untreated for metastatic disease with either synchronous or metachronous metastases are randomly assigned in a 1:1 ratio to resection of colorectal liver metastases followed by postoperative FOLFOX for 6 months or perioperative FOLFOXIRI and bevacizumab for 3 months pre- and postoperative and resection (PERIMAX), or to induction chemotherapy with FOLFOX and bevacizumab +/- irinotecan for a maximum of 6 months followed by maintenance treatment with fluoropyrimidine and bevacizumab. The primary objective of these trials is to evaluate the feasibility and efficacy of FOLFOXIRI and bevacizumab in metastatic colorectal cancer. Primary endpoint is failure free survival rate at 18 months in the PERIMAX trial and progression free survival rate at 9 months in CHARTA. Secondary objectives include efficacy, safety and tolerability.

Discussion: The CHARTA and PERIMAX trials are designed to evaluate the benefits and limitations of a highly active four-drug regimen in distinct treatment situations of metastatic CRC. Eligible patients are classified into resectable liver metastases to be randomized to perioperative treatment with FOLFOXIRI and bevacizumab or postoperative FOLFOX in the PERIMAX, or unresectable metastatic CRC to be randomized between FOLFOX and bevacizumab with or without irinotecan, stratified for clinical groups according to disease and patients' characteristics in the CHARTA trial.

Trial registration: Clinical trial identifier CHARTA: NCT01321957, PERIMAX: NCT01540435.

Figures

Figure 1
Figure 1
overview CHARTA trial.
Figure 2
Figure 2
overview PERIMAX trial.

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