NCT01461915

Phase 2 Study to Assess the Efficacy & Safety of Gemcitabine + Nab Paclitaxel With or Without Dociparstat in Metastatic Pancreatic Cancer Patients

A Randomized Phase II Open Label Study to Assess the Efficacy & Safety of Gemcitabine + Abraxane® With or Without ODSH (2-0, 3-0 Desulfated Heparin) as First Line Treatment of Metastatic Pancreatic Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Jazz Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This randomized, Phase 2, open label study aims to assess the efficacy and safety of gemcitabine + nab paclitaxel with or without dociparstat (ODSH) as first line treatment of metastatic pancreatic cancer. This study consists of 2 periods: a Run-in Period and a Randomized Period.

Detailed description

Dociparstat (ODSH) has demonstrated in vitro and in vivo inhibitory activity on mechanisms that are believed to play important roles in pancreatic cancer invasion, metastasis, and resistance to chemotherapy and radiation. Pancreatic cancer appears to have a dependence on autophagy, a regulated catabolic pathway to degrade and recycle cellular organelles and macromolecules. Autophagy appears to be largely driven by the binding of high mobility group box-1 protein (HMGB1) to the receptor for advanced glycation end-products (RAGE), which is strongly inhibited by dociparstat. Autophagy appears to not only assist pancreatic cancer cells to survive in a hypoxic, relatively avascular environment, but also appears to play an important role in chemotherapy resistance. Other important biological activities promoting pancreatic cancer invasion and metastasis affected by dociparstat include the inhibition of heparanase and the binding of tumor cells to endothelium and platelets mediated by the selectins. It is believed that these biological activities such as the inhibition of RAGE, heparanase, and selectin-mediated metastasis, can be inhibited by dociparstat at dose levels that can safely be administered without clinically significant anticoagulation. The standard of care of pancreatic cancer is evolving. It appears that 2 combination regimens, the "FOLFIRINOX" regimen (a combination of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin) and the combination of gemcitabine + nab-paclitaxel, could have more activity than the previous standard treatment of gemcitabine alone. Patients with advanced metastatic pancreatic cancer who have not received chemotherapy, surgical or radiation treatments and have a good performance status are eligible to participate in this study. This study consists of 2 periods: a Run-in Period and a Randomized Period. In total, 10 patients are planned to be enrolled in a Run-in Period to receive gemcitabine + nab-paclitaxel + dociparstat. Pharmacokinetic sampling and safety assessments are to be conducted to decide on the continuation to the Randomized Period of the study where 50 patients are planned to be randomized at a 1:1 ratio to either of the 2 study arms: * Arm A: Patients will receive gemcitabine + nab-paclitaxel + dociparstat * Arm B: Patients will receive gemcitabine + nab-paclitaxel The primary endpoint of this study is mean progression free survival. The secondary endpoints of this study are to consist of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, overall survival at the end of the study, and changes from baseline for carbohydrate antigen (CA) 19-9 marker, weight, and plasma albumin.

Conditions

• Metastatic Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	Nab paclitaxel	Nab-paclitaxel 125 mg/m2 will be administered IV over 30 minutes. Nab-paclitaxel will be administered weekly for 3 weeks followed by 1 week of rest (28-day cycle).
DRUG	Gemcitabine	Following the completion of nab-paclitaxel administration, gemcitabine IV infusion at 1000 mg/m2 will be administered over 30 minutes. Gemcitabine will be administered weekly for 3 weeks followed by 1 week of rest (28-cycle).
DRUG	Dociparstat	Following the completion of gemcitabine administration, dociparstat IV bolus at 4 mg/kg will be administered in 5 minutes immediately after completion of gemcitabine administration. Immediately following the dociparstat IV bolus administration, dociparstat 48-hour IV continuous infusion at 0.375 mg/kg/hr will be administered.

Timeline

• Start date: 2011-11-01
• Primary completion: 2012-12-01
• Completion: 2015-06-01
• First posted: 2011-10-28
• Last updated: 2022-06-06

Locations

16 sites across 1 country: United States