AUTHOR=Nakatsumi Hiroshi , Komatsu Yoshito , Muranaka Tetsuhito , Yuki Satoshi , Kawamoto Yasuyuki , Harada Kazuaki , Dazai Masayoshi , Tateyama Miki , Sasaki Yusuke , Miyagishima Takuto , Tsuji Yasushi , Katagiri Masaki , Nakamura Michio , Sogabe Susumu , Hatanaka Kazuteru , Meguro Takashi , Kobayashi Tomoe , Ishiguro Atsushi , Muto Osamu , Shindo Yoshiaki , Kotaka Masahito , Ando Takayuki , Takagi Ryo , Sakamoto Naoya , Sakata Yu 

TITLE=Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.939425

DOI=10.3389/fonc.2022.939425

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>The first-line chemotherapy for patients with <italic>RAS</italic> and <italic>BRAF</italic> wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies.</p></sec><sec><title>Methods</title><p>FOLFIRI (irinotecan 180 mg/m<sup>2</sup>, <italic>l</italic>-leucovorin 200 mg/m<sup>2</sup>, bolus 5-FU 400 mg/m<sup>2</sup>, and infusional 5-FU 2400 mg/m<sup>2</sup>/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi.</p></sec><sec><title>Discussion</title><p>There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy.</p></sec><sec><title>Clinical trial registration</title><p>Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, <uri xlink:href="https://jrct.niph.go.jp/latest-detail/jRCTs011190006" xmlns:xlink="http://www.w3.org/1999/xlink">https://jrct.niph.go.jp/latest-detail/jRCTs011190006</uri>.</p></sec>