Perioperative Treatment With Zoledronic Acid in Patients With Resectable Pancreas Cancer
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|ClinicalTrials.gov Identifier: NCT00892242|
Recruitment Status : Terminated (Principal Investigator decided to close the study early.)
First Posted : May 4, 2009
Last Update Posted : September 22, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma||Drug: Zoledronic acid||Phase 1|
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 process.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Perioperative Treatment With Zoledronic Acid in Patients With Resectable Pancreas Cancer|
|Study Start Date :||December 2009|
|Actual Primary Completion Date :||April 2013|
|Actual Study Completion Date :||April 2013|
Experimental: Neoadjuvant Zoledronic Acid
Zoledronic acid 4 mg IV prior to pancreatic resection (approximately 2 weeks prior to resection)
Zoledronic acid 4 mg IV monthly for two additional doses
Drug: Zoledronic acid
Other Name: Zometa
- Evaluate the safety and feasibility perioperative neoadjuvant zoledronic acid in patients with resectable pancreas cancer. [ Time Frame: 1 year postoperatively ]Rate of grade 3 and 4 toxicities, especially nephrotoxicity, electrolyte imbalance and osteonecrosis of the jaw.
- Evaluate whether treatment with perioperative zoledronic acid prolongs overall survival or disease free survival. [ Time Frame: 2 years ]
- Determine the pharmacodynamics on selected immune cell subgroups in the peripheral blood and marrow by flow cytometric analysis. [ Time Frame: Marrow (prior to first dose of zoledronic acid and week 10), peripheral blood (prior to first dose of zoledronic acid, week 10, and month 6) ]
- Determine the pharmacodynamics of neoadjuvant zoledronic acid therapy on selected immune cell subgroups in the tumor microenvironment by flow cytometric analysis of pancreatic tumor samples. [ Time Frame: Approximately week 2 (at time of surgery) ]
- Determine the pharmacodynamics of neoadjuvant zoledronic acid therapy on the neoangiogenesis. [ Time Frame: Prior to zoledronic acid treatment and then completion of zoledronic acid treatment (approximately 10 weeks) ]Surrogate markers of tumor-associated neoangiogenesis will be analyzed by ELISA. Serum levels of VEGF and MMP9 will be measured compared pre and post treatment.
- Determine the pharmacodynamics and surrogate markers neoangiogenesis analyzed by ELISA. [ Time Frame: Prior to zoledronic acid treatment and then completion of zoledronic acid treatment (approximately 10 weeks) ]Serum levels of VEGF and MMP9 will be measured compared pre and post treatment and the expression of VEGF and MMP9 in tumor samples will be analyzed.
- Measure the presence and change of micrometastatic disease present in the bone marrow at the time of surgery versus baseline using immunohistochemistry. [ Time Frame: Baseline and week 2 (time of surgery) ]
- Evaluate the clinical response and time to disease progression. [ Time Frame: 6 months postoperatively ]
- Correlate the presence of micrometastatic disease with time to recurrence and outcome. [ Time Frame: 6 months postoperatively ]
- Measure the change in the amount of micrometastatic disease from baseline. [ Time Frame: 6 months postoperatively ]
- Determine the pharmacodynamics of neoadjuvant zoledronic acid therapy on selected immune cell subgroups in the hepatic metastatic niche by flow cytometric analysis of pancreatic tumor samples [ Time Frame: Approximately 2 weeks (time of surgery) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00892242
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||David Linehan, M.D.||Washington University School of Medicine|