A Multicenter, Phase II Trial of the Safety and Efficacy of Amplimexon® (Imexon for Injection) in Combination With Taxotere® (Docetaxel) for Previously Treated Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)

Protocol AMP-024 is a Phase 2 study of imexon plus docetaxel for patients with previously treated lung cancer that has spread in the body. Docetaxel is approved by the Food and Drug Administration (FDA) as a second line therapy for this cancer. The imexon is administered on days 1-5 and the docetaxel on day 1 of every 3 week cycle. The objective of the protocol is to determine if the combination of imexon plus docetaxel is safe and effective.

开始日期2010-08-01

申办/合作机构

AmpliMed Corp.

NCT00637247 / Completed临床2期

A Phase 2 Randomized, Double-Blind, Multicenter Trial of Amplimexon® Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy Naïve Pancreatic Adenocarcinoma (Stage IV)

The purpose of this study is to determine if imexon in combination with gemcitabine could improve overall survival as compared to gemcitabine alone in subjects with pancreatic cancer that has spread to other organs such as the liver or lungs. The study will also look at the safety of the combination as compared to gemcitabine alone. Participants in the study will be randomly assigned to either treatment and neither the participant or their doctors will know which treatment they will be receiving.

开始日期2008-04-01

申办/合作机构

AmpliMed Corp.

NCT00327223 / Completed临床1期

A Phase 1 Trial of Amplimexon® (Imexon, Inj.) Administered Daily for 5 Days Every 3 Weeks to Patients With Metastatic Cancer or Disseminated Malignancy

AMP-011 is a Phase 1 study designed to extend the understanding of the toxicity and pharmacology of imexon by investigating a schedule of daily treatment for 5 days every three weeks. The objective of the study is to determine the maximally tolerated dose, the pharmacokinetics, and the toxicity of the drug on the designated schedule.

开始日期2005-11-01

申办/合作机构

AmpliMed Corp.

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0 项与 AmpliMed Corp. 相关的专利（医药）

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项与 AmpliMed Corp. 相关的文献（医药）

2018-03-01·American Journal of Clinical Oncology

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

Article

作者: Conkling, Paul ; Wong, Lucas ; Ma, Wen Wee ; Modiano, Manuel ; Pascual, Rolan ; Hersh, Evan ; Lee, Fa Chyi ; Nugent, Francis ; Zalupski, Mark M ; Cohen, Steven J

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/m2 days 1, 8, and 15 with either imexon, 875 mg/m2 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.

2012-11-14·Current Medicinal Chemistry2区 · 医学

Chemistry and Pharmacology of Imexon and Related Cyanoaziridines

2区 · 医学

Article

作者: Dorr, R. T. ; Remers, W. A.

Following the demonstration that addition of a 2-cyano group to aziridines prevented DNA alkylation and thus reduced toxicity, many novel 2-cyanoaziridines were synthesized and evaluated as immunomodulating and antitumor agents. They typically reacted with thiols such as cysteine, depleting them and allowing the accumulation of reactive oxygen species. Two of these compounds, azimexon and ciamexon, showed activity against tumors in clinical trials. Imexon was produced by cyclization of 2-cyanoaziridine-1- carboxamide in the presence of hydroxide ions. The two enantiomers were prepared by a process involving chiral chromatography. They were equipotent against cultured tumor cells. Imexon also reacts with thiols and it is especially potent against multiple myeloma in cell cultures. An efficient chemical synthesis and a lyophilization formulation of imexon as a water soluble, injectible drug, were developed. In Phase I and I/II clinical trials imexon showed hints of activity against a variety of tumors, but a randomized double-blind Phase II trial of imexon plus gemcitabine versus gemcitabine alone in pancreatic cancer showed no enhancement of activity above that of gemcitabine alone. This result was disappointing because in cell culture and mice the two compounds were synergistic. Based on a complete response in a Phase I trial, a new Phase II clinical trial of imexon is underway in non-Hodgkins lymphoma.

2012-04-01·Cancer Chemotherapy and Pharmacology4区 · 医学

Anti-tumor activity and mechanism of action for a cyanoaziridine-derivative, AMP423

4区 · 医学

Article

作者: Robert T. Dorr ; Lee Wisner ; Terry H. Landowski ; William A. Remers ; Betty K. Samulitis

PURPOSEPreclinical studies evaluated the anti-tumor activity and mechanism of action of AMP423, a naphthyl derivative of 2-cyanoaziridine-1-carboxamide with structural similarity to the pro-oxidant anti-tumor agent imexon.METHODSThe cytotoxic potency was evaluated in vitro against a variety of human cancer cell lines. Mechanism-of-action studies were performed in the human 8226/S myeloma cell line and its imexon-resistant variant, 8226/IM10. In vivo activity was evaluated against human myeloma and lymphoma xenografts in SCID mice. Pharmacokinetics and toxicology were investigated in non-tumor-bearing mice.RESULTSThe 72-h IC(50)s for all cell types ranged from 2 to 36 μM, across a wide variety of human cancer cell lines. AMP423 was active in SCID mice bearing 8226/S myeloma and SU-DHL-6 B-cell lymphoma tumors, with a median tumor growth delay (T-C) of 21 days (P = 0.0002) and 5 days (P = 0.004), respectively, and a median tumor growth inhibition (T/C) of 33.3% (P = 0.03) and 82% (P = 0.01), respectively. In non-tumor-bearing mice, AMP423 was not myelosuppressive. Mechanistic studies show that AMP423's mode of cell death is a mixture of necrosis and apoptosis, with generation of reactive oxygen species, inhibition of protein synthesis, and a decrease in reduced sulfhydryl levels, but no alkylation of nucleophiles. Unlike its structural analog imexon, which causes cell cycle arrest in G(2)/M, AMP423 induces the accumulation of cells in S-phase.CONCLUSIONSAMP423 has pro-oxidant effects similar to imexon, has greater cytotoxic potency in vitro, and has anti-tumor activity in hematologic tumors in vivo.

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药物(靶点)	适应症	全球最高研发状态

Ethonafide ( Top II )	肿瘤更多	终止
Imexon ( 核糖核苷酸还原酶复合体 )	转移性非小细胞肺癌更多	终止
AMP-423	血液肿瘤更多	终止
AMP-301	肿瘤更多	无进展