Archives: Clinical Trials

The overall goal of this feasibility study is to assess the initial safety and efficacy of LUM015 in ex vivo far-red imaging of colorectal, pancreatic, and esophageal cancers (adenocarcinoma) using the LUM Imaging System.

Traditional imaging techniques for insulinomas have a low detection rate. This study aims to evaluate the safety, internal radiation dosimetry, and targeted imaging capability of the novel GLP1R imaging agent, 68Ga-DOTA-SEMA, in patients with GLP1R-positive insulinomas.

Novel predictive markers are needed to determine treatment efficacy in pancreatic cancer at an early stage. Preferably, these markers could be determined non-invasively and provide insight into the biology of pancreatic cancer. Several MR techniques can serve for this purpose. However, optimalisation of these techniques is needed and their reproducibility should be assessed.

This study will investigate the tumor-associated vasculature of patients with solid tumors. The investigators will use a technology known as intravital microscopy (IVM) in order to visualize in real-time the vessels associated with solid tumors. The IVM observations may determine if an individual patient's tumor vessels would be amenable to receiving systemic therapy, based on the functionality of the vessels.

Accurate preoperative tumor detection and staging are fundamental for treating patients with pancreatic adenocarcinoma. Patients with unresectable tumors can benefit from being spared an extensive operation associated with substantial morbidity and mortality, cost, and pain. On the other hand, patients with localized disease, which is amenable to surgical removal, have the option of operation. Therefore, accurate staging of pancreatic cancer requires the detection of the tumor, and evaluation of its size, its relationship to major peri-pancreatic vascular structures and portal venous system, locoregional lymph nodes, and distant metastases. Multiple imaging techniques have been used to evaluate the pancreas. Although, at this point, no consensus exists as to the best staging algorithm, multidetector (MD) computed tomogrophy (CT) and Magnetic resonance imaging (MRI) provide sufficient information for the management of most patients.

Patients with a tumor larger than 3 cm are characterized as non-surgical. CT sensitivity in detecting small pancreatic tumors of less than 2 cm is low. Multiple methods have been suggested to increase the sensitivity of CT. The sensitivity of CT increases with using multidetector CT which now has an accuracy rate of about 95-97% for initial detection and approximating that of 100% for staging.

Secretin (a natural hormone produced by the duodenal mucosal cells) is known to increase blood flow to the pancreas. The principal use of secretin in imaging today is in exocrine function of the pancreas or morphological evaluation of the pancreatic duct under ultrasound or MRI. Theoretically, pancreatic contrast enhancement should also increase after secretin administration. This would imply that tumor conspicuity might also be increased if contrast enhancement of the normal pancreas increases. Secretin CT has been advocated by other centers to improve depiction of the ampulla and periampullary/duodenal diseases and to improve contrast enhancement. O'Connell et al, used secretin in patients suspected or with known pancreatic mass and concluded that administration of intravenous secretin leads to greater enhancement of the pancreas with greater tumor conspicuity, than imaging without secretin.

MRI of the pancreas has undergone a major change because it can provide noninvasive images of the pancreatic ducts and the parenchyma. MR cholangiopancreatography (MRCP) enables detection of anatomic variants such as pancreas divisum. Although contrast material-enhanced CT is still considered the gold standard in acute pancreatitis and for the detection of calcifications in chronic pancreatitis, MR imaging and secretin-enhanced MRCP are useful in evaluating pseudocysts and pancreatic disruption.

The role of MR is still debated in pancreatic neoplasms except the cystic lesions where MR imaging provides critical information regarding the lesion's content and a possible communication with the pancreatic ducts. Although some articles have shown that MRI was equivalent to CT in diagnosis and staging, others have shown the opposite. Nishiharu et al. found comparable tumor detection but a benefit with CT, notably for peripancreatic and vascular invasion. Comparing CT, echoendoscopy, and MRI, Soriano et al. demonstrated that CT showed the highest level of precision in primary tumor staging, local-regional staging, vascular invasion, distant metastases, Tumor, node, metastasis (TNM) staging, and tumor resectability. MRI retains its originality in imaging the parenchyma, the pancreatic and biliary ducts, and vascular structures; however, in many institutions, CT remains the reference imaging choice for diagnosing and staging pancreatic cancer. Other than CT's advantages for the tumor, its excellent spatial resolution also provides detailed reconstructions in all planes and arterial mapping and therefore makes it possible to search for surgical contraindications such as celiac trunk stenosis. MRI is still used today as a second-intention tool when there is doubt or when CT and echoendoscopy are not sufficiently conclusive; it is not currently recommended to use MRI in first-intention diagnosis of pancreatic cancer.

The aim of this pilot study is to determine whether the administration of intravenous secretin before contrast-enhanced CT and MRI improves pancreatic enhancement and pancreatic tumor conspicuity and to evaluate which technique is more appropriate for pancreatic tumor detection, staging and evaluation of resectability.

A. Pancreatic cancer background In 2012, 1,172 new pancreatic cancer patients were diagnosed in Switzerland. Only 20% of the patients with newly diagnosed pancreatic cancer are candidates for surgical resection, the only potential treatment for cure. Over 30% of the patients initially present with locally advanced disease. Patients with locally advanced disease have no evidence of metastatic spread to the liver, lung, and peritoneum but present with local involvement of vital structures that prohibits reasonable tumor resection. Currently, those patients are evaluated for palliative chemotherapy +/- radiation therapy. However, even with best conventional medical therapy, median survival of patients with locally advanced disease is mostly below 1 year. Over the last years, loco-regional therapies gained increased attention including radiofrequency-, cryo-, and microwave ablation as well as electrochemotherapy. However, all those entities are criticized by their complication rates leading to morbidity and mortality, limited area of application given the complex anatomical structures around the pancreas, and ill-defined improvements in overall survival.

B. Irreversible electroporation (IRE):

Irreversible electroporation is an emerging ablative modality that gained enormous interest over the last five years. For locally advanced pancreatic cancer, it was introduced in 2009. IRE is mainly non-thermal and primarily works through apoptosis. Its well studied safety profile allows ablation also within the context of locally advanced pancreatic cancer given it mainly spares vessels from destruction.

Increasing evidence shows that IRE for locally advanced, unresectable pancreatic cancer is effective compared to historic controls with a significant prolongation of local progression free survival, distant progression free survival and overall survival. The improvement in overall survival is about double the amount of what is seen with best new chemotherapy and chemoradiation regimens used at the present time. Those results are even more impressive given the discouraging improvements among palliative systemic options.

The NanoKnife IRE device (Angiodynamics, Queensbury, NY) is commonly used to perform IRE procedures in pancreatic cancer patients and is commercially available since 2009 and got Food and Drug Administration (FDA) 510K clearance for soft tissue ablation in October 2011 in the United States.

C. Quality of life and nutritional status/long term outcomes Given the overall poor long-term outcomes of patients with pancreatic cancer, health-related quality of life (HRQoL) measures are of utmost importance when treatment recommendations are discussed with patients. This is especially true for patients with more advanced staged disease where definitive surgical resection with curative intent is not possible. However, HRQoL reports for patients with locally advanced pancreatic cancer undergoing IRE are very limited. To the best of the investigators' knowledge, no other specific investigations exist that assessed HRQoL measures for patients undergoing IRE for locally advanced pancreatic cancer, no specific assessment exists that focuses on nutritional status for this patient group. In addition, impact on local and distant recurrence as well as cancer-specific and overall survival are still ill-defined and further information is needed.

The purpose of this study is to determine whether narrowband imaging (NBI) makes it easier for a surgeon to see cancer.

NBI is a kind of light. Normally, white light is used during surgery. White light uses many wavelengths of light. NBI only uses two wavelengths which highlight the blood vessels. This makes it easier for the surgeon to see blood vessels. Tumors often have more blood vessels than normal tissue. As a result, NBI may make it easier for the surgeon to see small tumors.

In this study the surgeon will look with both normal white light and NBI. This way a comparison can be made to determine which is superior.

Improved identification of tumors allows doctors and patients to make informed decisions about whether treatment is needed after surgery. It also provides additional information to determine which treatments may be best.

The purpose of ORACLE is to demonstrate the ability of a novel ctDNA assay developed by Guardant Health to detect recurrence in individuals treated for early-stage solid tumors. It is necessary that ctDNA test results are linked to clinical outcomes in order to demonstrate clinical validity for recurrence detection and explore its value in a healthcare environment subject to cost containment.

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with metastatic pancreatic cancer that did not respond to previous treatment with gemcitabine.

QUILT-3.088 NANT Pancreatic Cancer Vaccine: Phase II Randomized Trial of the NANT Pancreatic Cancer Vaccine vs. Standard-of-Care as First- Line Treatment for Patients with Metastatic Pancreatic Cancer.