Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer

Study Phase: Pilot study to assess nab-paclitaxel in combination with gemcitabine effects on pancreatic cancer stroma and tumor metabolism.

Study Objective(s):

A) Primary end-points:

• Evaluate the effect of nab-paclitaxel in combination with gemcitabine on tumor stroma density.
• Evaluate the effect of nab-paclitaxel on tumor vessels formation.
• Evaluate the effect of nab-paclitaxel on tumor metabolism.

B) Secondary end-point:

• Evaluate combination activity in relation with changes in tumor stroma and tumor metabolic activity.

The following studies will be performed prior and after treatment administration:

• 18FDG-PET/CT scan;
• Ultrasound Elastography;
• IHC:

• SPARC;
• Microvessel Density (CD-31, VEGF-A);
• Stroma density (SMA and Collagen I).

Study population and Number of subject: A total of 15 pancreatic cancer patients with resectable/resectable borderline disease are expected to be enrolled.

Study design and schedule: This is a pilot study to evaluate the effect of nab-paclitaxel on tumor stroma in pancreatic cancer patients. The study will be conducted in two parts:

Part A: Patients diagnosed with resectable/resectable pancreatic cancer will be screened for SPARC expression. Fifteen, SPARC positive patients, will be enrolled in the study and treated with nab-paclitaxel in combination with gemcitabine. Patients will be treated as follow:

• nab-paclitaxel will be administered at 125 mg/m2 as intravenous (i.v.) infusion over 30 minutes;
• followed by gemcitabine 1000 mg/m2 i.v. infusion over 30 minutes;

Treatment will be delivered weekly, for 3 weeks (on day 1, 8, and 15 over 28 days cycle) followed by a week of rest, for two cycles of treatment.

Part B: At the end of treatment tumors will be surgically resected according to standard surgical procedure for the treatment of pancreatic cancer.

Inclusion criteria

• Patients who are 18 years or older;
• Patients with resectable/resectable borderline pancreatic cancer;
• Adequate hematopoietic, hepatic and renal function:

• Neutrophil count > o = 1.5 x 109/L;
• Platelet count > o = 100 x 109/L;
• Bilirubin ≤ 1.5 x ULN;
• AST and/or ALT ≤ 2.5 x ULN;
• Serum creatinine ≤ 1.5 x ULN.
• Investigators must ensure that patients enrolled in the study will be available for all study procedures, including tumor biopsy, surgical treatment, and follow up.
• Investigators must ensure that patients have the ability to understand the requirements of the study and provide signed informed consent.
• Signed Informed Consent.

Exclusion criteria

• Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with patient eligibility for treatment;
• History of any psychiatric condition that might impair patient's ability to understand or to comply with the requirements of the study or to provide informed consent;
• Concurrent anticancer therapy;
• Pregnant or breast-feeding women (documented methods of birth control are required in those with reproductive potential);
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs;
• History of life threatening reaction to gemcitabine or abraxane;
• Previous exposure to other agents or treatment procedure as radiotherapy for the treatment of pancreatic cancer.