NCT00375310

Phase I Study of Gemcitabine, Sorafenib and Radiotherapy in Patients With Unresectable Pancreatic Cancer

Phase I Study of Gemcitabine With Novel RAF Kinase-Vascular Endothelial Growth Factor Receptor Inhibitor Sorafenib (BAY 43-9006) and Radiotherapy in Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: Indiana University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the safety and tolerability of the combined treatment of Sorafenib (BAY 43-9006) with Gemcitabine and radiotherapy in patients with localized unresectable pancreatic cancer.

Detailed description

Pancreatic cancer treatment is hampered by its resistance to both chemo and radiotherapy. Gemcitabine-based chemoradiotherapy has become one of the standard therapies for localized unresectable pancreatic cancer, but with poor responses and survival rates of less than 12 months. Radiotherapy increases VEGF expression and activates the Ras/MEK/ERK pathway which may contribute to radioresistance, thus the addition of anti-angiogenic agents and/or Ras/ERK inhibitors could enhance radiation mediated cytotoxicity. Sorafenib is a novel dual-action Raf kinase and vascular endothelial growth factor receptors (VEGF-R2 and VEGF-R3) inhibitor targeting both angiogenic and Ras-Raf-1 signal transduction pathways. Based upon preliminary laboratory and clinical data Sorafenib holds promise for improving outcomes of therapy for patients with locally advanced unresectable pancreatic cancer. Polymorphisms in genes involved in the angiogenesis pathway (VEGF, VEGF-R2, HIF-1 and eNOS) may contribute to the process of angiogenesis, tumor behavior, and may explain the heterogeneity in efficacy (and toxicity) of agents whose major mechanism of action is blocking angiogenesis33-37. Proteomic analysis may also contribute to identify patterns of response or resistance to therapies, and potentially predict outcomes. Dynamic contrast enhanced (DCE)-MRI has been shown to be a useful pharmacodynamic marker of biological activity for anti-angiogenic agents38-40 and may also predict radiation therapy-induced vascular changes41. In vivo imaging of angiogenesis using DCE-MRI and the analysis of angiogenesis markers genetic polymorphisms may predict response and clinical benefit to therapy for unresectable pancreatic cancer patients. These biologic and pharmacodynamic endpoints will be analysed to correlate with the tumor activity seen.

Conditions

• Pancreatic Cancer
• Adenocarcinoma of the Pancreas

Interventions

Type	Name	Description
DRUG	Gemcitabine, Sorafenib	Gemcitabine is given IV Sorafenib is given orally of varying doses: 1. Sorafenib 200 mg po qd ( during combination therapy) 2. Sorafenib 400 mg po qd ( during combination therapy) 3. Sorafenib 400 mg po bid ( during combination therapy)
PROCEDURE	Radiotherapy	1.8 Gy CTV daily for 5 weeks

Timeline

• Start date: 2006-09-01
• Primary completion: 2010-11-01
• Completion: 2014-11-01
• First posted: 2006-09-12
• Last updated: 2016-02-29

Locations

1 site across 1 country: United States