Effect On Tumor Perfusion Of A Chemotherapy Combining Gemcitabine And Nab-paclitaxel (Abraxane) In Pancreatic Cancer

Study Overview

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

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 ȭynamic" 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).

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.

Pancreatic Adenocarcinoma Resectable
Pancreatic Adenocarcinoma Locally Advanced
Pancreatic Adenocarcinoma Metastatic

DRUG: Gemcitabine
DRUG: Abraxane

2012-003592-19

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-10-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-09-02
First Submitted that Met QC Criteria 2012-10-24	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-09-04
First Posted (ACTUAL) 2012-10-26	Results First Posted N/A	Last Verified 2020-09

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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 patient	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) 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)

Participant Group/Arm

Intervention/Treatment

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 patient

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)

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)

Primary Outcome Measures	Measure Description	Time Frame
Dynamic tumor response rate as defined by a 40% modification of tumoral perfusion and cellular density parameters.	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.	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)

Secondary Outcome Measures	Measure Description	Time Frame
Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.	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)	12 months

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

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

Celgene Corporation

Investigators

PRINCIPAL_INVESTIGATOR: Jean-Luc Van Laethem, MD, PhD, Erasme University Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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