Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Effect on Tumor Perfusion of a Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Pancreatic Cancer (NEOPAX-001)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2012 by Erasme University Hospital
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Jean-Luc Van Laethem, Erasme University Hospital
ClinicalTrials.gov Identifier:
NCT01715142
First received: October 24, 2012
Last updated: NA
Last verified: October 2012
History: No changes posted
  Purpose

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with conventional treatments having little impact on disease course. Novel approaches are urgently needed to address inherent resistance to the current therapies and to identify new drugs or combinations that will have a high chance of success in pancreatic cancer patients. This proof-of-concept trial is studying the "dynamic" tumor response after the administration of a short course of gemcitabine and nab-paclitaxel (Abraxane) (a) during a window interval (4 weeks= 1 cycle) before surgery in resectable pancreatic cancer (cohort 1 = 21 patients) and (b) during at least 8 weeks (2 cycles) in locally advanced or metastatic pancreatic cancer (cohort 2 = 10 patients).


Condition Intervention Phase
Pancreatic Adenocarcinoma Resectable
Pancreatic Adenocarcinoma Locally Advanced
Pancreatic Adenocarcinoma Metastatic
Drug: Gemcitabine
Drug: Abraxane
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Tumoral Perfusion Modification by Dynamic Imaging After Chemotherapy Combining Gemcitabine and Nab-paclitaxel (Abraxane) in Patients With Potentially Operable, Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Erasme University Hospital:

Primary Outcome Measures:
  • Dynamic tumor response rate as defined by a 40% modification of tumoral perfusion and cellular density parameters. [ Time Frame: 4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients) ] [ Designated as safety issue: No ]
    In order to detect changes in the tumor microenvironment and to monitor treatment efficacy, Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) constitute tools more and more used. The acquired data can be analyzed using a pharmacokinetic model to obtain quantitative parameters relative to tissue perfusion and vascular permeability (Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space; Apparent Coefficient Diffusion as a surrogate marker of tissue cellularity). DCE/DW-MRI will be achieved before each chemotherapy treatment (and also before surgery for resectable patients). Each patient will be his/her own control by comparing serial imaging results with those of the baseline MRI.


Secondary Outcome Measures:
  • Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Number of participants with (serious) adverse events will be considered as a measure of safety of the whole therapeutic sequence (gemcitabine+Abraxane+surgery for resectable patients; gemcitabine+Abraxane for locally advanced/metastatic patients)


Other Outcome Measures:
  • Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: 4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients) ] [ Designated as safety issue: No ]
  • Effect of treatment on selected biomarkers in tumor resection specimens (cohort 1) and in case of obtaining tissue by Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) (cohort 2) [ Time Frame: 4 weeks (duration of 1 cycle of neoadjuvant chemotherapy for resectable patients); 8 weeks (duration of 2 cycles of treatment for locally advanced and metastatic patients) ] [ Designated as safety issue: No ]
    Evaluation of biomarkers involved in gemcitabine and nab-paclitaxel activity : human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), secreted protein acidic and rich in cysteine (SPARC), taxanes-related biomarkers.


Estimated Enrollment: 31
Study Start Date: December 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine+Abraxane
Chemotherapy combining gemcitabine and Abraxane during 4 weeks (1 cycle) before surgery (cohort 1: resectable patients) and during at least 8 weeks (2 cycles or more in case of response of stable disease) (cohort 2: locally advanced and metastatic patients)
Drug: Gemcitabine
Administrated intravenously at a dose of 1000 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)
Other Name: GEMZAR
Drug: Abraxane
Administrated intravenously at a dose of 125 mg/m2 over 30 minutes weekly, on day 1, day 8, day 15 followed by one week of rest (before surgery of before starting of the next cycle depending on the cohort allocation)
Other Name: nab-paclitaxel

Detailed Description:

Pancreatic cancer is a hypoperfused tumor, characterized by a high stroma density precluding cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for combining chemotherapy and antistromal drugs like nab-paclitaxel (Abraxane), a solvent (Cremophor® EL)-free, albumin-bound form of paclitaxel that has been initially developed to reduce the toxicities associated with Taxol injection while maintaining or improving its chemotherapeutic effect. This unique protein formulation provides a novel approach of increasing intra-tumoral concentrations of the drug by a receptor-mediated transport process allowing transcytosis across the endothelial cell.

Abraxane has been approved for commercialization in 38 countries, including the US, Canada, the EU, Australia, China, India and Korea for the treatment of women with metastatic breast cancer. Abraxane alone and in combination is being evaluated in a number of cancers, including metastatic melanoma, non-small cell lung cancer, pancreatic cancer and other solid tumors.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histo(cyto)logically proven ductal pancreatic adenocarcinoma;
  • Resectable or potentially resectable tumor; resectability assessed during a multidisciplinary meeting with expert surgeon and radiologist (cohort 1), or locally advanced and/or metastatic tumor (cohort 2);
  • First line chemotherapy;
  • Age > 18 years;
  • WHO performance status (PS) grade 0 or 1;
  • Absolute neutrophil count > 1.5 x 10 9 / L, platelets > 100 x 10 9/ L, creatinine clearance (Cockcroft and Gault formula) > 60 ml/min, haemoglobin level > 10 g/dl (transfusions authorized), bilirubin<1.5 g/dl;
  • Optimal biliary drainage;
  • Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation of who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum or urine pregnancy test prior to treatment. All WCBP, all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study;
  • Signed informed consent.

Exclusion Criteria:

  • Previous anticancer therapy for the pancreatic adenocarcinoma;
  • Biliary obstruction without endoscopic biliary drainage;
  • Any contre-indication for surgery;
  • Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the uterine cervix treated with a curative intent and any other tumor in complete remission with a disease-free interval > 3 years);
  • Uncontrolled congestive heart failure or angina pectoris, myocardial infarction within 1 year prior to study entry, uncontrolled hypertension (systolic pressure > 160 mm or diastolic pressure > 100 mm under well conducted antihypertensive treatment), QT prolongation;
  • Major uncontrolled infection;
  • Severe hepatic impairment;
  • Any medical, psychological, or social condition, which, in the opinion of the investigator, could hamper patient's compliance to the study protocol and/or assessment/interpretation of the data;
  • Pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods;
  • Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study; patients previously enrolled into this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01715142

Contacts
Contact: Jean-Luc Van Laethem, MD, PhD jl.vanlaethem@erasme.ulb.ac.be

Locations
Belgium
Antwerp University Hospital (UZA) Not yet recruiting
Edegem, Antwerpen, Belgium, 2650
Contact: Marc Peeters, MD,PhD       marc.peeters@uza.be   
Principal Investigator: Marc Peeters, MD, PhD         
Erasme University Hospital (ULB) Not yet recruiting
Brussels, Belgium, 1070
Contact: Jean-Luc Van Laethem, MD, PhD       jl.vanlaethem@erasme.ulb.ac.be   
Principal Investigator: Jean-Luc Van Laethem, MD, PhD         
Sub-Investigator: Raphaël Maréchal, MD, PhD         
Sub-Investigator: Anne Demols, MD, PhD         
Sponsors and Collaborators
Jean-Luc Van Laethem
Celgene Corporation
Investigators
Principal Investigator: Jean-Luc Van Laethem, MD, PhD Erasme University Hospital
  More Information

No publications provided

Responsible Party: Jean-Luc Van Laethem, MD, PhD, Erasme University Hospital
ClinicalTrials.gov Identifier: NCT01715142     History of Changes
Other Study ID Numbers: 2012-003592-19
Study First Received: October 24, 2012
Last Updated: October 24, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Erasme University Hospital:
Pancreatic cancer
Nab-paclitaxel
Gemcitabine
Neoadjuvant chemotherapy

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Gemcitabine
Paclitaxel
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014