A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma

Steven J. Cohen, Mark M. Zalupski, Paul Conkling, Francis Nugent, Wen Wee Ma, Manuel Modiano, Rolan Pascual, F. C. Lee, Lucas Wong, Evan M Hersh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND:: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS:: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS:: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS:: The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.

Original languageEnglish (US)
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
DOIs
StateAccepted/In press - Dec 24 2015

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gemcitabine
Multicenter Studies
Adenocarcinoma
Placebos
Drug Therapy
Confidence Intervals
Disease-Free Survival
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma. / Cohen, Steven J.; Zalupski, Mark M.; Conkling, Paul; Nugent, Francis; Ma, Wen Wee; Modiano, Manuel; Pascual, Rolan; Lee, F. C.; Wong, Lucas; Hersh, Evan M.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, 24.12.2015.

Research output: Contribution to journalArticle

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title = "A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-na{\"i}ve Pancreatic Adenocarcinoma",
abstract = "BACKGROUND:: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS:: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS:: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7{\%}), whereas 9 did in the placebo arm (17{\%}). In the imexon arm, 23 patients had ≥50{\%} reduction in CA 19-9 from baseline (33{\%}), whereas 22 did in the placebo arm (31.4{\%}). The median progression-free survival was 2.8 months in the imexon arm (95{\%} confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95{\%} CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95{\%} CI, 4.2-6.7 m) as compared with 6.8 m (95{\%} CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS:: The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.",
author = "Cohen, {Steven J.} and Zalupski, {Mark M.} and Paul Conkling and Francis Nugent and Ma, {Wen Wee} and Manuel Modiano and Rolan Pascual and Lee, {F. C.} and Lucas Wong and Hersh, {Evan M}",
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T1 - A Phase 2 Randomized, Double-Blind, Multicenter Trial of Imexon Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy-naïve Pancreatic Adenocarcinoma

AU - Cohen, Steven J.

AU - Zalupski, Mark M.

AU - Conkling, Paul

AU - Nugent, Francis

AU - Ma, Wen Wee

AU - Modiano, Manuel

AU - Pascual, Rolan

AU - Lee, F. C.

AU - Wong, Lucas

AU - Hersh, Evan M

PY - 2015/12/24

Y1 - 2015/12/24

N2 - BACKGROUND:: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS:: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS:: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS:: The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.

AB - BACKGROUND:: Imexon is a cyanoaziridine-derived iminopyrrolidone which has synergistic cytotoxicity with gemcitabine. A phase 1 study of the combination demonstrated good tolerance with encouraging clinical activity and thus we conducted this randomized phase II study. MATERIALS AND METHODS:: Patients with measurable, metastatic, treatment-naive pancreatic adenocarcinoma were randomized 1:1 to receive gemcitabine at 1000 mg/m days 1, 8, and 15 with either imexon, 875 mg/m or placebo days 1, 8, and 15 every 28 days. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and response rate. RESULTS:: A total of 142 patients were randomized, 72 to the imexon containing arm and 70 to the placebo arm. Patients in the imexon arm received an average of 3.6 cycles (range, 1 to 23) compared with 4.4 (range, 1 to 21) in the placebo arm. There was no increased rate of ≥grade 3 toxicity in the imexon arm. Seven patients had objective responses in the imexon arm (13.7%), whereas 9 did in the placebo arm (17%). In the imexon arm, 23 patients had ≥50% reduction in CA 19-9 from baseline (33%), whereas 22 did in the placebo arm (31.4%). The median progression-free survival was 2.8 months in the imexon arm (95% confidence interval [CI], 2.0-4.1 m) and 3.8 months in the placebo arm (95% CI, 2.2-4.7 m), P=0.504. The median overall survival time in the imexon arm was 5.2 months (95% CI, 4.2-6.7 m) as compared with 6.8 m (95% CI, 4.9-8.5 m) in the placebo arm, P=0.6822. CONCLUSIONS:: The combination of imexon and gemcitabine does not result in improved outcome as initial therapy of metastatic pancreatic adenocarcinoma.

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