Pancreatic Cancer Clinical Trials

Pancreatic clinical trials are research studies that evaluate whether a new drug, treatment, or combination of treatments is safe, effective and possibly better than the current standard-of-care.  They are important for cancer research and patient care as they are the only scientific way to prove whether a new treatment works better than current treatments.

For many people, particularly those whose cancer has not responded to standard treatments, it is important to consider all of your options.  A  clinical trial may be the best available treatment.

DNA changes in the pancreatic cells cause cancer

Inherited genes like BRCA2 and p16 can also increase the risk for developing pancreatic cancer

 Pancreatic Cancer

The pancreas is about 6 inches long, located behind the stomach and contains 2 different types of glands: exocrine and endocrine. The exocrine glands make pancreatic “juice,” which is released into the intestines. This juice contains enzymes that help digest the food you eat. Without these, some of the food would just pass through the intestines without being absorbed. The enzymes are released into tiny tubes called “ducts.” These tiny ducts merge to form larger ducts, which then empty into the pancreatic duct. The pancreatic duct merges with the common bile duct (the duct that carries bile from the liver), and empties the pancreatic juice into the duodenum (the first part of the small intestine) at the “ampulla of Vater.” More than 95% of the cells in the pancreas are in the exocrine glands and ducts, and the remaining 5% of cells in the pancreas are endocrine cells. These cells are in small clusters called “islets” (or “islets of Langerhans”). The islets make important hormones, such as insulin (reduces sugar) and glucagon (increases sugar), and release them directly into the blood.

Tumors of the exocrine cells are much more common than endocrine tumors and about 95% of the exocrine tumors are adenocarcinomas, which originate in the gland cells in the ducts.  Occasionally, they begin in the cells that pancreatic enzymes and therefore are called “acinar cell carcinomas.”  Other cancers of the exocrine pancreas include adenosquamous carcinomas, squamous cell carcinomas, signet ring cell carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with giant cells. Other distinctive pancreatic exocrine tumors include solid pseudopapillary neoplasms which are rare and usually occur in young women and ampullary cancer (cancer of Vater).

Endocrine pancreatic tumors are much less common than exocrine tumors, representing only 4% of tumors of the pancreas. These tumors are often called “pancreatic neuroendocrine tumors” (NETs) or islet cell tumors, and are classified as either functioning or non-functioning.  Functioning tumors, which are about half of the pancreatic NETs, make hormones that cause symptoms and the more common ones are gastrinomas (make gastrin), insulinomas (make insulin and are usually benign.  Non-functioning tumors do not create significant hormones and actually are more likely to be cancerous than functioning ones.  A third rare NET tumor is the carcinoid tumor, which is more common in other parts of the digestive system.

The treatment and outlook for pancreatic NETs depend on the specific tumor type and the stage (extent) of the tumor, but the outlook is generally better than that of pancreatic exocrine cancers. Learn more from the American Cancer Society

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Current Pancreatic Cancer Research

Pancreatic cancer researchers have been working to improve the treatment options for patients- including surgery, radiation and finding new and combined drug treatments.  They have learned that DNA changes in the pancreatic cells cause cancer, and that inherited genes like BRCA2 and p16 (responsible for a type of colon cancer) can also increase risk for developing pancreatic cancer. Discoveries such as this have opened the door to determining what other genes may be altered in pancreatic cancers that are not inherited. Also important is the discovery that pancreatic cancer develops over many years in a series of steps known as “pancreatic intraepithelial neoplasia” (PanIN). Early on (PanIn1), there are changes in a small number of genes, with no noticeable change in the duct cells, but later (PanIN 2 and PanIN 3), abnormalities in several genes are detected and the duct cells exhibit changes. Researchers are working on tests to better detect these gene changes prior to tumor growth. Once such example is that DNA changes that involve the KRAS oncogene, which affects the regulation of cell growth, can now be detected in pancreatic juice during the ERCP (endoscopic retrograde cholangiopancreatography) procedure, helping to detect earlier cancers. Learn more from the American Cancer Society

The Whipple procedure has long been the gold standard, but is a very complicated surgery with a long recovery time.  Minimally invasive surgery (also called “laparoscopic”) is an approach where the procedure is done through small incisions in the belly, a videoscope and instruments are inserted and the surgery is done via video visualization.  Patients have much shorter recovery time, but it is technically challenging.  Radiation is becoming more focused and options such as intraoperative radiation therapy (in which a single large dose of radiation is given to the pancreas in the operating room at the time of surgery) and proton beam radiation (which uses a special type of radiation that might do less damage to nearby normal cells) are being studied as well as radiation plus chemotherapy.

New drug combinations are being investigated, such as combining the gold standard gemcitabine with other drugs to improve overall survival.  One regimen under study is capecitabine (Xeloda) plus gemcitabine and another is the combination of gemcitabine, irinotecan, and celecoxib (an arthritis drug). Targeted therapies attack specific proteins on the cell surface that are unique to cancerous pancreatic cells and usually have fewer side effects than traditional chemotherapies. Pancreatic cancer cells also have defined molecules on their surface that allow them to grow “growth factor receptors.” Epidermal growth factor receptor (EGFR) is one that is currently the target of several drug studies because some patients with particular changes in the EGFR gene seem to respond better, and recently the first of these, Erlotinib (Tarceva), was approved in combination with gemcitabine. Other targets include blocking the growth of blood vessels that feed tumor growth, targeting tissue (called “stroma”) that surrounds the cancerous cells and seems to protect them. Learn more from the American Cancer Society

Immunotherapies are a recent development and mobilize the patient’s own immune system to attack cancer cells. Monoclonal antibodies are an example, and attach to a specific molecule on the surface of the pancreatic cancer cell, such as carcinoembryonic antigen (CEA). The antibody brings toxic substances into the tumor cells via this route, resulting in a direct treatment to cancerous cells and several are in current trials.  Other immunotherapies in clinical trials include therapeutic vaccines, checkpoint inhibitors/immune modulators, adoptive T cell transfer, adjuvant immunotherapies, and cytokines. Learn more from the Cancer Research Institute

Pancreatic cancer has been elusive over the years, but advances in earlier detection, less invasive surgical options, and the potential of immunotherapies and targeted therapies provides more hope to decrease side effects and improve overall survival for pancreatic cancer patients than ever before.

 History of Pancreatic Cancer Research

Pancreatic cancer is often detected in later stages, making it very challenging to treat. The signs and symptoms mimic other illnesses and its location behind other organs makes early diagnosis difficult.  Surgery has been recognized as the only curative treatment, but only 20% of patients can benefit because pancreatic cancer is often diagnosed too late. The gold standard surgical treatment is called the “Whipple” procedure, in which part of the pancreas, gallbladder, part of the stomach, part of the small intestine and part of the bile duct are removed. This surgery was recognized in 1935, when Allen Oldfather Whipple published the results of 3 surgical procedures in New York, which was the precursor to the modern Whipple procedure widely used today. Chemotherapy is offered for patients with both localized and advanced disease, and the first approved drug, gemcitabine, gained FDA approval in 1997 to improve quality of life and extended median survival by 5 weeks in patients who had surgery. In 2005, gemcitabine in combination with the targeted drug erlotinib (Tarceva), was proven to increase median overall survival for patients with locally advanced or metastatic pancreatic carcinoma. The FOLFIRINOX regimen, a combination of four drugs, was proven to be more effective that gemcitabine alone, but the side effects are increased, so is not suitable for many patients. Another option is nab-paclitaxel approved in 2013, which also exhibits increased side effects.  Radiation is often an option in cancer treatment, and has been utilized as both adjuvant therapy (in addition to surgery or chemotherapy) and palliative treatment, but no consensus has been reached on its effectiveness in pancreatic cancer. Learn more from the Cancer Research Institute

Advances in early detection, less invasive surgery and potential of immunotherapies and targeted therapies provides more hope for pancreatic cancer patients

Why Cure Forward?

Whether you’re seeking information about pancreatic cancer clinical trials or studies related to some other form of cancer, it can be hard to find trials that might be a good match.

Our Clinical Trial Exchange,collects data on clinical trials and studies from multiple sources making it easier to find all the options that are available. We work directly with clinical trial recruiters to bring current, active studies directly to you.  You can also select to be notified when new trials are added to ensure you are aware of all treatment options available.

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