Study protocol of the TRICOLORE trial: a randomized phase III study of oxaliplatin-based chemotherapy versus combination chemotherapy with S-1, irinotecan, and bevacizumab as first-line therapy for metastatic colorectal cancer.
BACKGROUND
Metastatic colorectal cancer carries a poor prognosis and cannot be cured by currently available therapy. Chemotherapy designed to prolong survival and improve the quality of life (QOL) of patients is the mainstay of treatment. Standard regimens of FOLFOX/bevacizumab and CapeOX/bevacizumab can cause neurotoxicity, potentially disrupting treatment. The results of 3 phase II studies of combination therapy with S-1, irinotecan, and bevacizumab showed comparable efficacy to mFOLFOX6/bevacizumab and CapeOX/bevacizumab, without severe neurotoxicity. Therefore, the establishment and evaluation of S-1-containing irinotecan-based regimens for first-line treatment are expected to become more important.


METHODS
The TRICOLORE trial is a multicenter, randomized, open-label, controlled phase III study which aims to evaluate the non-inferiority of combination therapy with S-1/irinotecan/bevacizumab (a 3-week regimen [SIRB] or 4-week regimen [IRIS/bevacizumab]) to oxaliplatin-based standard treatment (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) in patients with metastatic colorectal cancer who had not previously received chemotherapy. Patients will be randomly assigned to either the control group (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) or study group (SIRB or IRIS/bevacizumab). The target sample size is 450 patients. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), response rate (RR), time to treatment failure (TTF), relative dose intensity (RDI), the incidence and severity of adverse events, quality of life (QOL), quality-adjusted life years (QALY), health care costs, and relations between biomarkers and treatment response (translational research, TR).


CONCLUSIONS
The results of this study will provide important information that will help to improve the therapeutic strategy for metastatic colorectal cancer, and we believe that this study is very meaningful from the perspective of comparative effectiveness research.


BACKGROUND
UMIN000007834.
Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Kita-15 Nishi-7 Kita-ku, Sapporo, 060-8638, Japan. ykomatsu@ac.cyberhome.ne.jp.
Yoshito
Y
Komatsu
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. chikashi@idac.tohoku.ac.jp.
Chikashi
C
Ishioka
Department of Internal Medicine, Showa University Kouto Toyosu Hospital, 5-1-38 Toyosu, Kouto-ku, Tokyo, 135-8577, Japan. shimakenken60@hotmail.com.
Ken
K
Shimada
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. yayamada@ncc.go.jp.
Yasuhide
Y
Yamada
Department of Medical Oncology, Osaki Citizen Hospital, 2-3-10 Senjujicho, Hurukawa, Osaki Miyagi, 989-6183, Japan. m.gamoh-oc@h-osaki.jp.
Makio
M
Gamoh
Department of Medical Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifucho, Hirosaki, Aomori, 036-8562, Japan. sato1151@cc.hirosaki-u.ac.jp.
Atsushi
A
Sato
Department of Surgery, Tokyo Metropolitan Cancer and Infectious diseases Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. tatsuro@yamaguchi.email.ne.jp.
Tatsuro
T
Yamaguchi
Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Kita-15 Nishi-7 Kita-ku, Sapporo, 060-8638, Japan. satoshi-yuuki175@joy.ocn.ne.jp.
Satoshi
S
Yuki
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. smorita@kuhp.kyoto-u.ac.jp.
Satoshi
S
Morita
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. swt@idac.tohoku.ac.jp.
Shin
S
Takahashi
Hakubi Center of Advanced Research, Kyoto University, Yoshida-Ushinomiyacho, Sakyo-ku, Kyoto, 606-8501, Japan. goto.rei.7w@kyoto-u.ac.jp.|Graduate School of Economics, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto, 606-8501, Japan. goto.rei.7w@kyoto-u.ac.jp.
Rei
R
Goto
The Tokyo Cooperative Oncology Group, 2-1-18 Hamamatsu-cho, Minato-ku, Tokyo, 105-0013, Japan. kurihara@tcog.jp.
Minoru
M
Kurihara
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003362:Cost-Benefit Analysis; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D017048:Health Care Costs; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D011788:Quality of Life; D005641:Tegafur / Q000008:administration & dosage; D055815:Young Adult
D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin