A Trial Protocol of Biweekly TAS-102 and Bevacizumab as Third-Line Chemotherapy for Advanced/Recurrent Colorectal Cancer: A Phase II Multicenter Clinical Trial (The TAS-CC4 Study)

Yoichiro Yoshida; Takeshi Yamada; Hiroshi Matsuoka; Hiromichi Sonoda; Atsuko Fukazawa; Hiroshi Yoshida; Hideyuki Ishida; Keiji Hirata; Suguru Hasegawa; Kazuhiro Sakamoto; Toshiaki Otsuka; Keiji Koda

doi:10.23922/jarc.2018-043

A Trial Protocol of Biweekly TAS-102 and Bevacizumab as Third-Line Chemotherapy for Advanced/Recurrent Colorectal Cancer: A Phase II Multicenter Clinical Trial (The TAS-CC4 Study)

J Anus Rectum Colon. 2019 Jul 30;3(3):136-141. doi: 10.23922/jarc.2018-043. eCollection 2019.

Authors

Affiliations

¹ Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
² Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
³ Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan.
⁴ Department of Surgery, Shiga University of Medical Science, Shiga, Japan.
⁵ Department of Gastroenterological Surgery, Iwata City Hospital, Shizuoka, Japan.
⁶ Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁷ Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁸ Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.
⁹ Department of Hygiene and Public Health, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
¹⁰ Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.

Abstract

Background: Treatment with TAS-102 has significantly improved the progression-free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC). Reportedly, the combination of TAS-102 plus bevacizumab extends the median PFS. The present study aimed to confirm the efficacy and safety of TAS-102 plus bevacizumab (biweekly administration) as third-line chemotherapy for patients with mCRC.

Methods/design: This is a single-arm, open-label, prospective, nonrandomized, multicenter phase II trial conducted in Japan. With a threshold and expected PFS of 2.1 and 3.5 months, respectively, the simulation results showed a sample size of 42 with α = 0.05 (both sides) for 90% power, based on the One-Arm Binomial test using the SWOG statistical tool. If the estimated dropout is 7%-8%, the target sample size is estimated to be 45. The TAS-CC4 study regimen comprised 28-day cycles with biweekly oral administration of TAS-102 (35 mg/m² twice daily on days 1-5 and 15-19 of every 28-day cycle) and bevacizumab (5.0 mg/kg on days 1 and 15). The primary end point is the PFS; secondary end points include response rate (RR), OS, grade ≥3 neutropenia, and genetic alterations (KRAS/BRAF mutations) in the circulating cell-free DNA.

Discussion: The present study can contribute to the determination of the effective dosing interval of TAS-102 and bevacizumab in patients with mCRC and is thought to lead to prophylaxis of neutropenia and prolongation of the treatment period.

Keywords: TAS-102; biweekly administration; colorectal cancer; neutropenia.