Phase I Study of Single Dose Neoadjuvant Zoledronic Acid in Patients With Resectable Pancreas Cancer
Cancer of the pancreas carries an ominous prognosis. The five-year overall survival rate of
this malignancy is less than 5%. Chemotherapy with gemcitabine carries a response rate of
approximately 25%. Resection offers the only potential for cure; however, even with
resection, the great majority of patients will die with metastatic disease. Substantial
improvements are needed in the treatment of this malignancy.
Patients with this disease process have clearly developed a tolerance to their pancreatic
tumor. This is evidenced by an increased number and activity immunosuppressive cells
including MDSC and Treg in patients with pancreas cancer. An intervention that inhibits
this population of MDSC and Treg may be highly useful in the treatment of this disease
A novel treatment of pancreas cancer, in this setting, would be to deplete circulating and
tumor-associated immunosuppressive cells prior to resection. This would facilitate the host
to mount a greater immune response against the tumor. The eventual goal would be to combine
neoadjuvant zoledronic acid with gemcitabine, another agent which synergizes with zoledronic
acid to target MDSC. When combined with current adjuvant chemoradiation, the use of
zoledronic acid in the neoadjuvant and adjuvant setting, it is hoped that the patient could
mount a greater immune response leading to increased overall survival through the prevention
of local disease and distant metastasis.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the safety and feasibility perioperative neoadjuvant zoledronic acid in patients with resectable pancreas cancer. To evaluate whether treatment with perioperative zoledronic acid prolongs overall survival or disease free survival.
David Linehan, M.D.
Washington University School of Medicine
United States: Institutional Review Board
09-0589 / 201109094
|Washington University School of Medicine||Saint Louis, Missouri 63110|