Safety, Pharmacokinetics and Efficacy of AXP107-11 in Combination With Standard Gemcitabine (Gemzar®) Treatment in Patients With Locally Advanced or Metastatic, Unresectable, Adenocarcinoma of the Pancreas, Stage III-IV: A Prospective, Open Label, Multi-centre, Sequential Phase Ib/IIa Study

The purpose of this study is to assess the effect and safety of AXP107-11 alone, and in combination with gemcitabine standard therapy, in patients with advanced or metastatic cancer of the pancreas. The safety, pharmacokinetics and efficacy of AXP107-11 in these patients will also be studied.

Start Date01 Nov 2010

Sponsor / Collaborator

Axcentua Pharmaceuticals AB

EUCTR2010-019214-25-SE / Not yet recruitingPhase 1/2

Safety, pharmacokinetics and efficacy of AXP107-11 in combination with standard gemcitabine (Gemzar®) treatment in patients with locally advanced or metastatic, unresectable, adenocarcinoma of the pancreas, stage III-IV. A prospective, open label, multi-centre, sequential phase Ib/IIa study.

Start Date24 Aug 2010

Sponsor / Collaborator

Axcentua Pharmaceuticals AB

100 Clinical Results associated with Axcentua Pharmaceuticals AB

0 Patents (Medical) associated with Axcentua Pharmaceuticals AB

Literatures (Medical) associated with Axcentua Pharmaceuticals AB

01 Jul 2016·PancreatologyQ3 · MEDICINE

A phase I dose escalation trial of AXP107-11, a novel multi-component crystalline form of genistein, in combination with gemcitabine in chemotherapy-naive patients with unresectable pancreatic cancer

Q3 · MEDICINE

Article

Author: Karimi, Masoud ; Löhr, Johannes-Matthias ; Verbeke, Caroline Sabine ; Berkenstam, Anders ; Kartalis, Nikolaos ; Frödin, Jan-Erik ; Omazic, Brigitta

BACKGROUNDAXP107-11 is a novel, multi-component crystalline form of the naturally occurring compound genistein. AXP107-11 has improved physiochemical properties and oral bioavailability compared to the natural form of genistein, and it is possible that combining AXP107-11 with chemotherapy may increase the effect and reduce chemoresistance. The purpose of this dose escalation phase Ib study was to assess the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of AXP107-11 in combination with gemcitabine in treatment-naïve patients with inoperable pancreatic carcinoma.PATIENTS AND METHODSAXP107-11 was given orally in escalating doses (400 mg-1600 mg daily) in combination with standard gemcitabine treatment (1000 mg/m(2)/week) for the first seven of eight weeks and thereafter for a maximum of four × four-week treatment cycles. PK, safety, MTD and efficacy of AXP107-11 in combination with gemcitabine were evaluated.RESULTSSixteen patients were enrolled and received AXP107-11. The maximum concentration in serum of unconjugated (free) genistein was 1 μM. Neither dose-limiting toxicities (DLTs) nor signs of hematological or non-hematological toxicities related to AXP107-11 were observed over a period ranging from 0.7 to 13.2 months. The median overall survival time was 4.9 months (range 1.5-19.5 months). Seven patients (44%) survived longer than six months and 19% were alive at the one-year follow-up.CONCLUSIONTreatment of pancreatic cancer patients with AXP107-11 in combination with gemcitabine resulted in a favorable PK-profile with high serum levels without signs of either hematological or non-hematological toxicity. Accordingly, we suggest further studies with AXP107-11 in pancreatic cancer patients.

01 Dec 2014·AtherosclerosisQ2 · MEDICINE

The thyroid receptor β modulator GC-1 reduces atherosclerosis in ApoE deficient mice

Q2 · MEDICINE

Article

Author: Gåfvels, M ; Kannisto, K ; Webb, P ; Eggertsen, G ; Rehnmark, S ; Parini, P ; Larsson, L ; Slätis, K

Thyroid hormone reduces plasma cholesterol and increases expression of low-density lipoprotein receptor (LDL-R) in liver, an effect mediated by thyroid receptor β (TRβ). The selective TRβ modulator GC-1 also enhances several steps in reverse cholesterol transport and can decrease serum cholesterol independently of LDL-R. To test whether GC-1 reduces atherosclerosis and to determine which mechanisms are active, we treated ApoE deficient mice with atherogenic diet ± GC-1. GC-1 reduced cholesteryl esters in aorta after 20 weeks. Serum free and esterified cholesterol were reduced after 1 and 10 weeks, but not 20 weeks. Hepatic bile acid synthesis and LDL-R expression was elevated after 1, 10 and 20 weeks, without changes in hepatic de novo cholesterol synthesis. GC-1 increased faecal neutral sterols and reduced serum campesterol after 1 week, indicating reduced intestinal cholesterol absorption. After 20 weeks, GC-1 increased faecal bile acids, but not faecal neutral sterols. Hepatic scavenger receptor B1 (SR-B1) expression was decreased by GC-1. We conclude that GC-1 delays the onset of atherosclerosis in ApoE deficient mice. Since ApoE is needed for hepatic cholesterol reabsorption by LDL-R, this supports the idea that GC-1 reduces serum cholesterol independently of LDL-R by increasing hepatic bile acid synthesis. GC-1 lipid-lowering effects in ApoE deficient mice may also be partly due to reduced intestinal cholesterol absorption. Since reductions in serum cholesterol are reversed at longer times, these GC-1 dependent effects may not be enough for sustained cholesterol reduction in long term treatments.

15 Apr 2012·Cancer Research

Abstract 4244: The role of hypoxia on the tumor-stromal interaction in pancreatic ductal adenocarcinoma

Author: Löhr, Matthias ; Heuchel, Rainer L. ; Longati, Paola ; Wagman, Annika ; Witt, Michael R. ; Jia, Xiaohui ; Jesenofsky, Ralf

AbstractINTRODUCTION: Pancreatic cancer is characterized by extraordinary fibrosis and pancreatic stellate cells (PSCs) are the major player in synthesizing extracellular matrix (ECM) upon activation. The interaction/communication between PSCs and pancreatic ductal adenocarcinoma (PDAC) cells is essential for inducing stroma/ECM production, pancreatic cancer progression and general therapy resistance. Compared to traditional 2D cell culture, cells in a three-dimensional context demonstrate different behavior and functions as reflected by building up a microenvironment that more closely mimics the one observed in the native tissue. This feature is especially critical for testing drug efficiency as cellular response to drugs is profoundly affected by environmental cues. AIMS & METHODS: Our aim was to build up a more reliable and predictive drug screening system. To this end we set up and compared 2D and 3D cell cultures containing either human PSC and PDAC cells alone or in combination. RESULTS: Among PDAC cells, panc-1 cells are the most commonly used which are also able to form spheres in vitro. We generated mono-spheres from panc-1 cells and compared them to conventional 2D culture. The efficiency of different drugs on viability of cells in panc-1 sphere resulted to be much lower than on viability in 2D cultures. Cells in 3D compared to the 2D culture show higher gene expression for ECM proteins as collagen and fibronectin, for growth factors as PDGF and VEGF, as well as for protein like Cox2, Glut1. We co-cultured panc-1 and PSCs, allowing them to interact and form hetero-spheres in which PSCs localized in the cortical area and were identified e.g. by expression of asma, a marker for PSCs activation. These avascular mini-tumors were further characterized at different levels. CONCLUSION: 3D cultures are more resistant to chemotherapy compared to their 2D counterpart offering a more predictive platform for drug screening before proceeding to more expensive in vivo models and clinical trials. The avascular mini-tumors can be considered as an alternative in vitro cell model for studying pancreatic cancer development and fibrosis from a more complete perspective.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4244. doi:1538-7445.AM2012-4244

100 Deals associated with Axcentua Pharmaceuticals AB

100 Translational Medicine associated with Axcentua Pharmaceuticals AB

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Genistein sodium dihydrate(Axcentua Pharmaceuticals AB) ( ERβ )	Pancreatic Cancer More	Phase 2
AXP-107-16	Genital Diseases, Female More	Pending
AXP-107-08	Wounds and Injuries More	Pending
Genistein ( Top II x Tyrosine kinase )	Adenocarcinoma More	Pending
AXP-107-17	Radiation Injuries More	Pending

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