A Study in Second Line Metastatic Colorectal Cancer

Summary

The purpose of this study is to compare overall survival in participants with metastatic colorectal cancer treated with either ramucirumab and FOLFIRI or placebo and FOLFIRI.

Timeline

Start

2010-12-02

Primary completion

2014-07-17

Completion

2016-06-20

Outcome

Met primary endpoint

registry Ramucirumab + FOLFIRI vs Placebo + FOLFIRI; p = 0.0219; Hazard Ratio (HR) 0.844 (95% CI 0.730 to 0.976); Log Rank NCT01183780 ↗

paper INTERPRETATION: Ramucirumab plus FOLFIRI significantly improved overall survival compared with placebo plus FOLFIRI as second-line treatment for patients with metastatic colorectal carcinoma. PMID 25877855 ↗

release “RAISE trial, a Phase III study of ramucirumab (CYRAMZA™) in combination with chemotherapy in patients with metastatic colorectal cancer (mCRC), met its primary endpoint” lilly.com ↗

release “Phase III study of Cyramza® in combination with chemotherapy in patients with metastatic colorectal cancer met its primary endpoint of overall survival.” lilly.com ↗

Publications

• Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.
• Taniguchi H, Yoshino T, Yamaguchi K, Yamazaki K, Nixon AB, Tabernero J, Van Cutsem E, Robling KR, Abada PB, Hozak RR, Siegel R, Fill JA, Wijayawardana S, Walgren RA, Giles B, Jones A, Pitts KR, Drove N, Muro K. Clinical development and evaluation of a VEGF-D assay in plasma from patients with metastatic colorectal cancer in the RAISE study. Curr Med Res Opin. 2021 Oct;37(10):1769-1778. doi: 10.1080/03007995.2021.1940908. Epub 2021 Jul 28.
• Lim HH, Hopkins AM, Rowland A, Yuen HY, Karapetis CS, Sorich MJ. Effect of Early Adverse Events on Survival Outcomes of Patients with Metastatic Colorectal Cancer Treated with Ramucirumab. Target Oncol. 2019 Dec;14(6):743-748. doi: 10.1007/s11523-019-00683-z.
• Yoshino T, Portnoy DC, Obermannova R, Bodoky G, Prausova J, Garcia-Carbonero R, Ciuleanu T, Garcia-Alfonso P, Cohn AL, Van Cutsem E, Yamazaki K, Lonardi S, Muro K, Kim TW, Yamaguchi K, Grothey A, O'Connor J, Taieb J, Wijayawardana SR, Hozak RR, Nasroulah F, Tabernero J. Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase III study. Ann Oncol. 2019 Jan 1;30(1):124-131. doi: 10.1093/annonc/mdy461.
• Grothey A, Yoshino T, Bodoky G, Ciuleanu T, Garcia-Carbonero R, Garcia-Alfonso P, Van Cutsem E, Muro K, Mytelka DS, Li L, Lipkovich O, Hsu Y, Sashegyi A, Ferry D, Nasroulah F, Tabernero J. Association of baseline absolute neutrophil counts and survival in patients with metastatic colorectal cancer treated with second-line antiangiogenic therapies: exploratory analyses of the RAISE trial and validation in an electronic medical record data set. ESMO Open. 2018 Apr 24;3(3):e000347. doi: 10.1136/esmoopen-2018-000347. eCollection 2018.
• Tabernero J, Hozak RR, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu TE, Portnoy DC, Prausova J, Muro K, Siegel RW, Konrad RJ, Ouyang H, Melemed SA, Ferry D, Nasroulah F, Van Cutsem E. Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Ann Oncol. 2018 Mar 1;29(3):602-609. doi: 10.1093/annonc/mdx767.
• Obermannova R, Van Cutsem E, Yoshino T, Bodoky G, Prausova J, Garcia-Carbonero R, Ciuleanu T, Garcia Alfonso P, Portnoy D, Cohn A, Yamazaki K, Clingan P, Lonardi S, Kim TW, Yang L, Nasroulah F, Tabernero J. Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression. Ann Oncol. 2016 Nov;27(11):2082-2090. doi: 10.1093/annonc/mdw402. Epub 2016 Aug 29.
• Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu TE, Portnoy DC, Van Cutsem E, Grothey A, Prausova J, Garcia-Alfonso P, Yamazaki K, Clingan PR, Lonardi S, Kim TW, Simms L, Chang SC, Nasroulah F; RAISE Study Investigators. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015 May;16(5):499-508. doi: 10.1016/S1470-2045(15)70127-0. Epub 2015 Apr 12.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ramucirumab	Monoclonal antibody	8 mg/kg	Intravenous
Background	Irinotecan	Small molecule	180 mg/m2	Intravenous
Background	Leucovorin	Small molecule	400 mg/m2	Intravenous
Background	fluorouracil	Small molecule	2400 mg/m2	Intravenous

Indications