Anti-EGFR antibodies (Panitumumab (Pmab)/Cetuximab (Cmab)) have established efficacy and manageable safety profiles either in monotherapy or in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC) patients (pts). In recent global phase III RECOURCE study, TAS-102 significantly improved OS and PFS over placebo for mCRC pts refractory to standard therapies. In preclnical models, the combination of Pmab with TAS-102 demonstrated enhanced activities compared with either drug alone. This phase I/II study is designed to investigate the safety and efficacy of Pmab combination with TAS-102 for pts with RAS (KRAS/NRAS) wild-type mCRC refractory to standard chemotherapy.
Eligible pts are aged 20-74 y, ECOG performance status 0-1 with histologically/cytologically confirmed RAS wild-type mCRC, and refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin, and anti-angiogenesis therapy and had neither prior anti-EGFR antibody nor regorafenib treatment. Phase I part is designed to determine recommended phase II dose (RP2D) in the dose de-escalation design of Pmab (6 mg/kg) every 2 weeks combination with TAS-102 (35 mg/m2 BID on days 1–5 and 8–12, every 4 weeks). The primary objectives are to evaluate the incidence proportion of DLTs (phase I) and to evaluate the investigator assessed PFS rate at 6 months (phase II). In order to evaluate the effect of TAS-102 in addition to Pmab monotherapy, an exact binomial test with a nominal one-sided 5% significance level was predicted to have at least 80% power to detect the difference between the null hypothesis proportion of 29% PFS rate and the alternative proportion of 48% PFS rate with the sample size of 47 patients. To assure an adequate number of evaluable patients, target number of subjects are defined 52 (addition to Phase I patients administered with RP2D). As of May 2016, 6 pts have been enrolled. Results are expected in 2017.
Clinical trial identification
Legal entity responsible for the study
Takeda pharmaceutical Co., ltd.
K. Yamaguchi: Honoraria (speaker's bureau): Takeda, Taiho, Merch, Chugai, Eli-Lily: Research funding for clinical trials from Takeda. Y. Komatsu: Honoraria (speaker's bureau) and Research funding from Novartis, Pfizer, Bayer, Yakult, Daiichi-Sankyo, Kyowa-Kirin, Chugai, Merck-Serono, BMS, Taiho, Takeda, Eli-Lilly. E. Oki: has received Honoraria (lecture fee) from Takeda, Taiho. T. Yoshino: Research funding for clinical trials from GlaxoSmithKline, Boehringer Ingelheim. K. Yamazaki: Honoraria (lecture and/or manuscript fee) from Bayer, Yakult, Daiichi-Sankyo, Chugai, Merck-Serono, BMS, Taiho, Takeda. Research funding from BMS. K. Shibuya: Employee of Takeda. K. Oba: Honoraria (lecture and/or manuscript fee) from Takeda, BMS, Ono, Chugai. T. Kato: Honoraria (lecture fee) from Bayer, Yakult, Chugai, Merck-Serono, Takeda.