TY - JOUR
T1 - Rationale for and Design of the PARADIGM Study
T2 - Randomized Phase III Study of mFOLFOX6 Plus Bevacizumab or Panitumumab in Chemotherapy-naïve Patients With RAS (KRAS/NRAS) Wild-type, Metastatic Colorectal Cancer
AU - Yoshino, Takayuki
AU - Uetake, Hiroyuki
AU - Tsuchihara, Katsuya
AU - Shitara, Kohei
AU - Yamazaki, Kentaro
AU - Oki, Eiji
AU - Sato, Takeo
AU - Naitoh, Takeshi
AU - Komatsu, Yoshito
AU - Kato, Takeshi
AU - Yamanaka, Kazunori
AU - Iwasaki, Kouji
AU - Soeda, Jumpei
AU - Hihara, Masamitsu
AU - Yamanaka, Takeharu
AU - Ochiai, Atsushi
AU - Muro, Kei
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/6
Y1 - 2017/6
N2 - Background It remains unclear whether an anti-VEGF or anti-EGFR antibody with standard doublet chemotherapy is the optimal first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC). Here we outline the PARADIGM study (NCT02394795), designed to evaluate the superiority of panitumumab over bevacizumab, in combination with oxaliplatin/5-fluorouracil/leucovorin (mFOLFOX6) in patients with RAS wild-type chemotherapy-naïve mCRC. Patients and Methods Eligible patients are aged 20 to 79 years with an ECOG performance status of 0-1 and histologically/cytologically confirmed RAS wild-type mCRC. A total of 800 patients are to be randomly assigned (1:1 ratio) to mFOLFOX6 plus panitumumab (n = 400) or bevacizumab (n = 400) and stratified according to institution, age (20-64 vs. 65-79 years), and liver metastases (present vs. absent). Each treatment regimen includes oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, and 5-fluorouracil (5-FU) I.V. 400 mg/m2 on day 1; 5-FU continuous I.V. 2400 mg/m2 on days 1 to 3; and either panitumumab 6 mg/kg or bevacizumab 5 mg/kg on day 1 every 2 weeks. The primary endpoint is overall survival forming the basis to detect a hazard ratio of 0.76 with a 1-sided type I error rate of 0.025 and 80% power. Secondary efficacy endpoints include progression-free survival, response rate, duration of response, and curative resection rate. A comprehensive biomarker analysis (NCT02394834) using archival tumor tissue and circulating tumor DNA samples collected at different time points (pretreatment and confirmed progressive disease) will investigate potential biomarkers related to primary and secondary resistance. The first patient was enrolled in May 2015 and the study is anticipated to complete in 2020.
AB - Background It remains unclear whether an anti-VEGF or anti-EGFR antibody with standard doublet chemotherapy is the optimal first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC). Here we outline the PARADIGM study (NCT02394795), designed to evaluate the superiority of panitumumab over bevacizumab, in combination with oxaliplatin/5-fluorouracil/leucovorin (mFOLFOX6) in patients with RAS wild-type chemotherapy-naïve mCRC. Patients and Methods Eligible patients are aged 20 to 79 years with an ECOG performance status of 0-1 and histologically/cytologically confirmed RAS wild-type mCRC. A total of 800 patients are to be randomly assigned (1:1 ratio) to mFOLFOX6 plus panitumumab (n = 400) or bevacizumab (n = 400) and stratified according to institution, age (20-64 vs. 65-79 years), and liver metastases (present vs. absent). Each treatment regimen includes oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2, and 5-fluorouracil (5-FU) I.V. 400 mg/m2 on day 1; 5-FU continuous I.V. 2400 mg/m2 on days 1 to 3; and either panitumumab 6 mg/kg or bevacizumab 5 mg/kg on day 1 every 2 weeks. The primary endpoint is overall survival forming the basis to detect a hazard ratio of 0.76 with a 1-sided type I error rate of 0.025 and 80% power. Secondary efficacy endpoints include progression-free survival, response rate, duration of response, and curative resection rate. A comprehensive biomarker analysis (NCT02394834) using archival tumor tissue and circulating tumor DNA samples collected at different time points (pretreatment and confirmed progressive disease) will investigate potential biomarkers related to primary and secondary resistance. The first patient was enrolled in May 2015 and the study is anticipated to complete in 2020.
KW - Anti-EGFR
KW - Anti-angiogenesis
KW - Clinical trial
KW - Overall survival
KW - VEGF
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U2 - 10.1016/j.clcc.2017.01.001
DO - 10.1016/j.clcc.2017.01.001
M3 - Article
C2 - 28237539
AN - SCOPUS:85013418974
VL - 16
SP - 158
EP - 163
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
SN - 1533-0028
IS - 2
ER -