The Role of the Tumor Microenvironment of Pancreatic Cancer to Predict Treatment Outcome

Summary

Pancreatic cancer is a highly lethal disease. Patients with resectable or borderline resectable disease may benefit from preoperative radiochemotherapy. However, only a subset of patients will respond to this potentially toxic and expensive treatment. Therefore, novel predictive markers are needed to determine treatment efficacy at an early stage. Preferably, these markers could be determined non-invasively and provide insight into the biology of pancreatic cancer. Pancreatic cancers are heterogeneous tumors. The tumor microenvironment is often characterized by large amounts of stroma, hypovascularization, and hypoxia. As these three factors can all contribute to treatment resistance, a quantitative assessment of these markers may aid in the prediction of response to preoperative radiochemotherapy. Moreover, these assessments may have prognostic value. Finally, further insight into the interrelation of these aspects of the tumor microenvironment can contribute to the evaluation of new targeted treatment options. Tumor cellularity and extracellular matrix composition can be assessed non-invasively in vivo by diffusion weighted magnetic resonance imaging (DWI) and tumor vascularity can be assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Finally, tumor hypoxia can be evaluated by T2\* MRI and PET-CT, using the 18F-labeled hypoxic marker HX4.

Objective of the study:

The primary aim of the study is to assess whether DWI, DCE-MRI, T2\*, and 18F-HX4-PET/CT predict overall survival in patients with pancreatic cancer treated with surgery and adjuvant chemotherapy or with neoadjuvant radiochemotherapy, surgery and adjuvant chemotherapy. Secondary aims of the study include the assessment of the predictive value of DWI, DCE-MRI, T2\*, and 18F-HX4-PET/CT for pathological response to neoadjuvant chemoradiation, the correlation of DWI, DCE-MRI, T2\*, and 18F-HX4-PET/CT with histopathological assessment of tumor stroma, vascularization, and hypoxia, and the assessment of the predictive value of these histopathological markers for overall survival.

Conditions

• Pancreatic Cancer

Interventions

DRUG

Gadobutrol

0.1 ml/kg Gadovist is administered at 5 ml/s followed by a 15 ml saline flush

DRUG

[F-18]HX4

400 MBq \[F-18\]HX4, is administered in a single intravenous bolus injection, followed by a saline flush.

DRUG

Gemcitabine

1000 mg/m2/dose on day 1 and 8 in 2 cycles of 21 days (three weeks) each, one cycle before and one cycle after radiochemotherapy. During radiotherapy gemcitabine is administered at 1000 mg/m2/dose on day 1, 8 and 15.

RADIATION

Radiotherapy

A hypofractionated scheme of 15 fractions of 2.4 Gy in three weeks will be applied, combined with the second course of gemcitabine.

PROCEDURE

Pancreaticoduodenectomy

Sponsors & Collaborators

• Erasmus Medical Center

  collaborator OTHER

• Dutch Cancer Society

  collaborator OTHER

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-11-30

Primary Completion

2017-12-31

Completion

2017-12-31

Countries

• Netherlands

Study Locations