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

Pancreatic Cancer research study

What is the primary objective of this study?

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.

Who is eligible to participate?

Inclusion Criteria: - Patients with pancreatic tumors, with histological or cytological proof of adenocarcinoma or a high suspicion on CT imaging. - Tumor size ≥ 1cm. - WHO-performance score 0-2. - Scheduled for surgery or neo-adjuvant chemotherapy/radiation followed by surgery. For the reproducibility part of the study, patients who will not undergo surgery, may be included, too. - Written informed consent. Exclusion Criteria: - Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol. - Contra-indications for MR scanning, including patients with a pacemaker, cochlear implant or neurostimulator; patients with non-MR compatible metallic implants in their eye, spine, thorax or abdomen; or a non-MR compatible aneurysm clip in their brain; patients with severe claustrophobia. - Renal failure (GFR < 30 ml/min) hampering safe administration of Gadolinium containing MR contrast agent. - For the reproducibility part of the protocol: surgery, radiation and/or chemotherapy foreseen within the timeframe needed for MR scanning.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Pancreatic Cancer

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Gadobutrol0.1 ml/kg Gadovist is administered at 5 ml/s followed by a 15 ml saline flush

Drug:[F-18]HX4400 MBq [F-18]HX4, is administered in a single intravenous bolus injection, followed by a saline flush.

Drug:Gemcitabine1000 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:RadiotherapyA hypofractionated scheme of 15 fractions of 2.4 Gy in three weeks will be applied, combined with the second course of gemcitabine.

Procedure:Pancreaticoduodenectomy

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Neoadjuvant radiochemotherapyPatients elected for neoadjuvant radiochemotherapy undergo DWI-MRI, DCE-MRI (Gadobutrol),T2*-MRI and [F-18]HX4 PET/CT imaging within two weeks before start of the chemoradiation and again after radiochemotherapy (Gemcitabine/Radiotherapy), within two weeks before surgery (Pancreaticoduodenectomy).

Primary SurgeryPatients elected for primary surgery undergo DWI-MRI, DCE-MRI (Gadobutrol),T2*-MRI and [F-18]HX4 PET/CT imaging within two weeks before surgery (Pancreaticoduodenectomy).

Study Status

Completed

Start Date: November 2013

Completed Date: December 2017

Phase: N/A

Type: Interventional

Design:

Primary Outcome: Predictive value of pretreatment DWI, DCE-MRI, T2*, and 18F-HX4-PET/CT on overall survival in patients with pancreatic cancer treated with surgery and adjuvant chemotherapy or with neoadjuvant radiochemotherapy, surgery and adjuvant chemotherapy.

Secondary Outcome: Predictive value of pretreatment DWI, DCE-MRI, T2*, and 18F-HX4-PET/CT on recurrence free survival in patients with pancreatic cancer treated with surgery and adjuvant chemotherapy or with neoadjuvant radiochemotherapy, surgery and adjuvant chemotherapy.

Study sponsors, principal investigator, and references

Principal Investigator:

Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Collaborator: Erasmus Medical Center

More information:https://clinicaltrials.gov/show/NCT01989000

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