Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Gemcitabine plus nab-paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring nab-paclitaxel, neoadjuvant treatment, SPARC, Pancreatic Cancer
Eligibility 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.
Sites / Locations
- Centro Integral Oncologico Clara Campal
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Gemcitabine plus nab-paclitaxel
Arm Description
This is a single arm study.
Outcomes
Primary Outcome Measures
Effect of nab-paclitaxel on pancreatic cancer stroma, new vessel formation and tumor cell metabolism.
Primary End-point:
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 by PET-CT scan measuring pre-treatment versus post-treatment glucose uptake.
Secondary Outcome Measures
Activity of nab-paclitaxel in combination with gemcitabine against PDA in relation with changes in tumor stroma and tumor metabolic activity.
To assess secondary end-point the following studies will be performed
18FDG-PET/CT scan;
Ultrasound Elastography;
IHC:
SPARC;
Microvessel Density (CD-31, VEGF-A);
Stroma density (SMA and Collagen I).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01442974
Brief Title
Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
Official Title
Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Grupo Hospital de Madrid
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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:
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:
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:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
nab-paclitaxel, neoadjuvant treatment, SPARC, Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gemcitabine plus nab-paclitaxel
Arm Type
Experimental
Arm Description
This is a single arm study.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine plus nab-paclitaxel
Other Intervention Name(s)
Gemzar, 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate, Abraxane, ABI007
Intervention Description
Gemcitabine 1000mg/mq on d1,8,15 over 28 days of cycle nab-paclitaxel 125mg/mq on d1,8,15 over 28 days cycle Treatment will be administered for two cycles
Primary Outcome Measure Information:
Title
Effect of nab-paclitaxel on pancreatic cancer stroma, new vessel formation and tumor cell metabolism.
Description
Primary End-point:
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 by PET-CT scan measuring pre-treatment versus post-treatment glucose uptake.
Time Frame
up to 18 months
Secondary Outcome Measure Information:
Title
Activity of nab-paclitaxel in combination with gemcitabine against PDA in relation with changes in tumor stroma and tumor metabolic activity.
Description
To assess secondary end-point the following studies will be performed
18FDG-PET/CT scan;
Ultrasound Elastography;
IHC:
SPARC;
Microvessel Density (CD-31, VEGF-A);
Stroma density (SMA and Collagen I).
Time Frame
up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manuel Hidalgo, MD, PhD
Organizational Affiliation
Centro Integral Oncologico Clara Campal (CIOCC), Centro National Investigacion Oncologica (CNIO)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro Integral Oncologico Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
12. IPD Sharing Statement
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Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
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