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

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ClinicalTrials.gov Identifier: NCT01442974
Recruitment Status : Completed
First Posted : September 29, 2011
Last Update Posted : March 13, 2013
Sponsor:
Information provided by (Responsible Party):
Sofia Perea, Director Clinical Trials Unit., Grupo Hospital de Madrid

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.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Gemcitabine plus nab-paclitaxel Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Assessment Of Stromal Response To Nab-Paclitaxel In Combination With Gemcitabine In Pancreatic Cancer
Study Start Date : January 2011
Actual Primary Completion Date : January 2012
Actual Study Completion Date : June 2012


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
  • 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate
  • Abraxane
  • ABI007




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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): NCT01442974


Locations
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Spain
Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
Sponsors and Collaborators
Grupo Hospital de Madrid
Investigators
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Principal Investigator: Manuel Hidalgo, MD, PhD Centro Integral Oncologico Clara Campal (CIOCC), Centro National Investigacion Oncologica (CNIO)

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Responsible Party: Sofia Perea, Director Clinical Trials Unit., Director Clinical Research Unit, Grupo Hospital de Madrid
ClinicalTrials.gov Identifier: NCT01442974     History of Changes
Other Study ID Numbers: ABX271-PA09EU
First Posted: September 29, 2011    Key Record Dates
Last Update Posted: March 13, 2013
Last Verified: March 2013
Keywords provided by Sofia Perea, Director Clinical Trials Unit., Grupo Hospital de Madrid:
nab-paclitaxel
neoadjuvant treatment
SPARC
Pancreatic Cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs