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

Primary Purpose

Pancreatic Adenocarcinoma Resectable, Pancreatic Adenocarcinoma Locally Advanced, Pancreatic Adenocarcinoma Metastatic

Status

Completed

Phase

Early Phase 1

Locations

Belgium

Study Type

Interventional

Intervention

Gemcitabine

Abraxane

About this trial

This is an interventional treatment trial for Pancreatic Adenocarcinoma Resectable focused on measuring Pancreatic cancer, Nab-paclitaxel, Gemcitabine, Neoadjuvant chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Antwerp University Hospital (UZA)
Erasme University Hospital (ULB)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gemcitabine+Abraxane

Arm Description

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)

Outcomes

Primary Outcome Measures

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.

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.

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)

Full Information

NCT ID

NCT01715142

First Posted

October 24, 2012

Last Updated

September 2, 2020

Sponsor

Jean-Luc Van Laethem

Collaborators

Celgene Corporation

1. Study Identification

Unique Protocol Identification Number

NCT01715142

Brief Title

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

Acronym

NEOPAX-001

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

March 21, 2013 (Actual)

Primary Completion Date

September 21, 2015 (Actual)

Study Completion Date

April 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Jean-Luc Van Laethem

Collaborators

Celgene Corporation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Adenocarcinoma Resectable, Pancreatic Adenocarcinoma Locally Advanced, Pancreatic Adenocarcinoma Metastatic

Keywords

Pancreatic cancer, Nab-paclitaxel, Gemcitabine, Neoadjuvant chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Gemcitabine+Abraxane

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

GEMZAR

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Abraxane

Other Intervention Name(s)

nab-paclitaxel

Intervention Description

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 Measure Information:

Title

Dynamic tumor response rate as defined by a 40% modification of tumoral perfusion and cellular density parameters.

Description

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)

Secondary Outcome Measure Information:

Title

Number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0.

Description

Time Frame

12 months

Other Pre-specified Outcome Measures:

Title

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)

Title

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)

Description

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.

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jean-Luc Van Laethem, MD, PhD

Organizational Affiliation

Erasme University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Antwerp University Hospital (UZA)

City

Edegem

State/Province

Antwerpen

ZIP/Postal Code

2650

Country

Belgium

Facility Name

Erasme University Hospital (ULB)

City

Brussels

ZIP/Postal Code

1070

Country

Belgium

12. IPD Sharing Statement

Learn more about this trial

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

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