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

March 12, 2013 updated by: Sofia Perea, Director Clinical Trials Unit., Grupo Hospital de Madrid

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28050
        • Centro Integral Oncologico Clara Campal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Gemcitabine plus nab-paclitaxel
This is a single arm study.
Drug: Gemcitabine plus nab-paclitaxel
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
Other Names:
  • Gemzar
  • Abraxane
  • 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate
  • ABI007

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of nab-paclitaxel on pancreatic cancer stroma, new vessel formation and tumor cell metabolism.
Time Frame: up to 18 months

Primary End-point:

  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 by PET-CT scan measuring pre-treatment versus post-treatment glucose uptake.
up to 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Activity of nab-paclitaxel in combination with gemcitabine against PDA in relation with changes in tumor stroma and tumor metabolic activity.
Time Frame: up to 18 months

To assess secondary end-point the following studies will be performed

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

  • IHC:

    1. SPARC;
    2. Microvessel Density (CD-31, VEGF-A);
    3. Stroma density (SMA and Collagen I).
up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grupo Hospital de Madrid

Investigators

  • Principal Investigator: Manuel Hidalgo, MD, PhD, Centro Integral Oncologico Clara Campal (CIOCC), Centro National Investigacion Oncologica (CNIO)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (ACTUAL)

January 1, 2012

Study Completion (ACTUAL)

June 1, 2012

Study Registration Dates

First Submitted

June 13, 2011

First Submitted That Met QC Criteria

September 28, 2011

First Posted (ESTIMATE)

September 29, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

March 13, 2013

Last Update Submitted That Met QC Criteria

March 12, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ABX271-PA09EU

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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