Efficacy and Safety of Simtuzumab (SIM) With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma

Summary

The primary objective of this study is to compare the additive efficacy of SIM versus placebo in combination with leucovorin (folinic acid), irinotecan, and fluorouracil (FOLFIRI) as measured by improvement in progression-free survival (PFS) in participants with metastatic KRAS mutant colorectal adenocarcinoma who have progressed following a first-line oxaliplatin- and fluoropyrimidine-containing regimen.

Timeline

Start

2011-12

Primary completion

2014-10

Completion

2015-02

Outcome

Missed primary endpoint

registry FOLFIRI + Placebo (Part B) vs FOLFIRI + SIM 200 mg (Part B); p = 0.0395; Hazard Ratio (HR) 1.45 (95% CI 1.01 to 2.06) NCT01479465 ↗

paper The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma. PMID 28246207 ↗

Publications

• Hecht JR, Benson AB 3rd, Vyushkov D, Yang Y, Bendell J, Verma U. A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic KRAS Mutant Colorectal Adenocarcinoma. Oncologist. 2017 Mar;22(3):243-e23. doi: 10.1634/theoncologist.2016-0479. Epub 2017 Feb 28.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Simtuzumab	Monoclonal antibody	200 mg	Intravenous
Subject	Simtuzumab	Monoclonal antibody	700 mg	Intravenous
Background	Irinotecan	Small molecule	180 mg/m2	Intravenous
Background	Leucovorin	Small molecule	200 mg/m2	Intravenous
Background	Leucovorin	Small molecule	400 mg/m2	Intravenous
Background	fluorouracil	Small molecule	400 mg/m2	Intravenous
Background	fluorouracil	Small molecule	2400 mg/m2	Intravenous

Indications