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

NCT01715142 | Completed Early Phase 1

• 1 other identifier: 2012-003592-19
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

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).

Conditions

Pancreatic Adenocarcinoma Resectable; Pancreatic Adenocarcinoma Locally Advanced; Pancreatic Adenocarcinoma Metastatic

Keywords

Pancreatic cancer; Nab-paclitaxel; Gemcitabine; Neoadjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  12 months

Other Outcomes (2)

• Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  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)

• 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)

  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)

Study Arms (1)

Gemcitabine+Abraxane

EXPERIMENTAL

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; Drug: Abraxane

Interventions

Gemcitabine DRUG

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)

Also known as: GEMZAR

Gemcitabine+Abraxane

Abraxane DRUG

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)

Also known as: nab-paclitaxel

Gemcitabine+Abraxane

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jean-Luc Van Laethem: lead
• Celgene Corporation: collaborator

Study Sites (2)

Antwerp University Hospital (UZA)

Edegem, Antwerpen, 2650, Belgium

Location

Erasme University Hospital (ULB)

Brussels, 1070, Belgium

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Jean-Luc Van Laethem, MD, PhD

  Erasme University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: October 26, 2012
• Study Start: March 21, 2013
• Primary Completion: September 21, 2015
• Study Completion: April 30, 2017
• Last Updated: September 4, 2020

Record last verified: 2020-09

Locations

BE (2)