Nimotuzumab in Adults With Pancreatic Cancer
CHEMOTHERAPY-NAIVE PATIENTS WITH LOCALLY ADVANCED OR METASTATIC PANCREATIC CANCER
Pancreatic Cancer, Advanced or Metastatic
|Official Title:||A RANDOMIZED, MULTICENTER, PHASE IIB/IIIA STUDY OF GEMCITABINE AND THE MONOCLONAL ANTIBODY NIMOTUZUMAB (OSAG 101) VERSUS GEMCITABINE AND PLACEBO FOR THE TREATMENT OF CHEMOTHERAPY-NAIVE PATIENTS WITH LOCALLY ADVANCED OR METASTATIC PANCREATIC CANCER|
- Time to tumor progression (TTP) and overall survival (OS) in chemotherapy-naive patients. To assess the efficacy of Nimotuzumab as add on therapy to Gemcitabine in comparison with Gemcitabine and placebo [ Time Frame: Week 8, 12 ]
- To evaluate the objective tumor response (overall response rate [ORR]) and duration of response (DR) To evaluate the safety profile of Nimotuzumab in combination with Gemcitabine To evaluate quality of life (QoL) according to EORTC [ Time Frame: Week 8, 16 ]
|Study Start Date:||September 2007|
|Estimated Study Completion Date:||March 2013|
Active Comparator: Nimotuzumab
Placebo Comparator: Placebo
Pancreatic cancer is responsible for 227.000 deaths per year, and is the eighth most common cause of death from cancer in both sexes combined, a position relatively high when compared to incidence (thirteenth position) because of the very poor prognosis (the M/I ratio is 98%) (Global Cancer Statistics, 2002). The incidence of pancreatic carcinoma has increased almost 300% since 1950 and now exceeds the incidence of stomach cancer and cancer of the rectum. Carcinoma of the exocrine pancreas is nearly always a fatal disease. The overall 5-year survival rate for the disease is 4.1%.
Locally advanced or metastatic pancreatic cancer is relatively unresponsive to chemotherapy. Gemcitabine therapy provides some benefit and modestly improves survival compared with fluorouracil, but median survival in patients with advanced disease remains less than 6 months (Burris et al, 1997). Cytotoxic drug combinations were not able to show survival advantage compared to Gemcitabine alone in numerous randomized phase III studies.
Altered expression or constitutive activation of the epidermal growth factor receptor (EGFR/HER1/erbB1) commonly occurs in both primary and metastatic pancreatic cancers and is often a critical factor in progressive growth and resistance to normal mechanisms of cell death. Epidermal growth factor receptor expression in pancreatic cancer has been correlated with tumor aggressiveness.
Clinical trials already suggest that EGF-R targeted therapy may improve the antitumor activity of chemotherapy for treatment of pancreatic carcinoma. Monoclonal antibodies specific to EGF-R can be combined safely and effectively with chemotherapy.
Nimotuzumab (OSAG101, hR3, Theraloc) is a humanized monoclonal antibody (mAb) that binds to the EGFR. In preclinical studies the antibody has shown potent antitumor activity. Based on phase I data, the recommended dose has been established at 200 mg weekly. A previous phase II study in children with high grade brain tumors showed activity of Nimotuzumab as a monotherapeutic agent, even in prognostic very unfavourable diffuse, intrinsic pontine glioma. No drug related side effects were reported.
Nimotuzumab (OSAG101, Theraloc) in combination with radiotherapy for treatment of locally advanced squamous cell carcinomas of the head and neck resulted in high rates of antitumor response, and was accompanied by a favourable safety profile. Nimotuzumab (OSAG101, Theraloc) has a high hepatic uptake level.
This randomized, placebo-controlled Phase IIb/IIIa study analyzes the efficacy and safety of Nimotuzumab in combination with Gemcitabine for the treatment of chemotherapy-naive patients with advanced unresectable or metastatic pancreatic carcinoma.
|Herne, Germany, 44621|
|Principal Investigator:||Dirk Strumberg, MD||University Bochum|