Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
Information source: Grupo Hospital de Madrid
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pancreatic Cancer
Intervention: Gemcitabine plus nab-paclitaxel (Drug)
Phase: N/A
Status: Completed
Sponsored by: Grupo Hospital de Madrid Official(s) and/or principal investigator(s): Manuel Hidalgo, MD, PhD, Principal Investigator, Affiliation: Centro Integral Oncologico Clara Campal (CIOCC), Centro National Investigacion Oncologica (CNIO)
Summary
Targeting tumor stroma is emerging as a strategic approach for pancreatic cancer treatment.
Actually, one of the most interesting characteristics of pancreatic cancer is the dense
fibrotic stroma surrounding tumor cells. Moreover, pancreatic cancer stroma seems to express
a specific protein profile different from tumor cells. For example, secreted protein rich in
cysteine (SPARC) is overexpressed in pancreatic tumor stroma fibroblast and downregulated in
tumor cells. This characteristic is associated with poor clinical outcome.
Nab-paclitaxel, an albumin bound nano formulation of paclitaxel that targets SPARC,
decreases tumor stroma density. Such effect improves drug delivery, and enhances both,
nab-paclitaxel and gemcitabine, antitumor activity in nude mouse models.
Based on this pre-clinical data the investigators designed a clinical trial of
nab-paclitaxel in combination with gemcitabine as neo-adjuvant treatment for pancreatic
cancer patients. Fifteen, SPARC positive patients, will be enrolled in the study and treated
with abraxane in combination with gemcitabine.
This is a pilot study which primary end point is evaluating the effect of Abraxane in
combination with gemcitabine on tumor stroma, and the secondary end-point is correlating
these changing with treatment activity.
Clinical Details
Official title: Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Effect of nab-paclitaxel on pancreatic cancer stroma, new vessel formation and tumor cell metabolism.
Secondary outcome: Activity of nab-paclitaxel in combination with gemcitabine against PDA in relation with changes in tumor stroma and tumor metabolic activity.
Detailed description:
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:
1. Evaluate the effect of nab-paclitaxel in combination with gemcitabine on tumor stroma
density.
2. Evaluate the effect of nab-paclitaxel on tumor vessels formation.
3. Evaluate the effect of nab-paclitaxel on tumor metabolism.
B) Secondary end-point:
1. 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:
1. SPARC;
2. Microvessel Density (CD-31, VEGF-A);
3. 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Centro Integral Oncologico Clara Campal, Madrid 28050, Spain
Additional Information
Starting date: January 2011
Last updated: March 12, 2013
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