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
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 ODSH. 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 ODSH 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 ODSH at dose levels that can safely be
administered without clinically significant anticoagulation.
The standard of care of pancreatic cancer is evolving. It appears that two 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.
Subjects with advanced metastatic pancreatic cancer that have not received chemotherapy,
surgical or radiation treatments and have a good performance status will be eligible to
participate in this study. 10 patients will be enrolled in a Run-in Period to receive
gemcitabine + nab-paclitaxel +ODSH. PK sampling and safety assessments will be conducted to
decide on the continuation to the Controlled Period of the study where 50 patients will be
randomized at a 1:1 ratio to either of the two study arms: Arm A will receive gemcitabine +
nab-paclitaxel + ODSH and Arm B will receive gemcitabine + nab-paclitaxel.
The primary endpoint of the study is mean progression free survival. The secondary
endpoints consist of tumor response by RECIST criteria, overall survival at the end of the
study and changes from baseline for CA19-9 marker, weight and plasma albumin.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-Free Survival (PFS) according to RECIST Guidelines.
Median Progression-Free Survival according to RECIST Guidelines Version 4.03
From Baseline to disease progression or death (whichever occurs first), assessed up to 9 months.
Mitesh J Borad, MD
Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic , Scottsdale Arizona
United States: Food and Drug Administration
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|University of Texas Medical Branch||Galveston, Texas 77555-1329|
|South Texas Oncology & Hematology||San Antonio, Texas 78207|
|Mayo Clinic Arizona||Scottsdale, Arizona 85259|
|Medical University of South Carolina Hollings Cancer Center||Charleston, South Carolina 29425|
|Saint Mary's Health Care||Grand Rapids, Michigan 49503|
|Cleveland Clinic Florida||Weston, Florida 33331|
|UPMC Cancer Center||Pittsburgh, Pennsylvania 15232|
|Disney Family Cancer Center||Burbank, California 91505|
|Marin Cancer Care||Greenbrae, California 94904|
|Scripps Clinic Torrey Pines ( Green Hospital)||La Jolla, California 92037|
|Loyola University Medical Center/Cardinal Bernardin Cancer Center||Maywood, Illinois 60153|
|Indiana University Health, Goshen Center for Cancer Care||Goshen, Indiana 46526|
|Fesit-Weiller Cancer Center||Shreveport, Louisiana 71130|
|Summa Health System - Cooper Cancer Center||Akron, Ohio 44304|
|Thomas Jefferson University [Kimmel Cancer Center]||Philadelphia, Pennsylvania 19107|