While we’ve already learned a lot about neuroendocrine tumors (NETs) and adopted a range of therapies, more work remains. At Penn Medicine, we’re focused on answering scientific questions about these complex tumors and developing new and improved treatments. We conduct extensive research and run a growing and diverse portfolio of clinical trials.
We always consider where clinical trials may fit into the full scope of your treatment. While we offer a number of studies — many based at Penn — we can also help you find options at other programs based on your personalized treatment needs.
Understanding Clinical Trials for Neuroendocrine Tumors
Neuroendocrine tumors often grow slowly, even when they metastasize (spread). That pace means people may choose to travel for specialized care, including clinical trials. We welcome you to reach out about one of our trials, even if you do not receive your care here.
Researchers design clinical trials to confirm safety and measure the effectiveness of emerging treatments. Participating in a trial may offer you a treatment option and the chance to play a role in innovation. You can make a meaningful contribution to moving the NET field forward.
NET clinical trials look to develop new therapies or refine existing approaches. They also test new treatment combinations and sequences. Many studies focus on drug therapy for neuroendocrine tumors. While doctors can already turn to a range of NET treatments when surgery is not enough, there’s still room for improvement and further options.
Establishing Promising NET Clinical Trials at Penn
We have a proven track record with clinical trial leadership, introducing new treatments and influencing national guidelines.
Our doctors were lead investigators in national trials that led to the first-ever nonsurgical option for pheochromocytoma and paraganglioma, known as pheo-para. They served in a similar role for successful trials of peptide receptor radionuclide therapy (PRRT) — a type of nuclear medicine for NETs.
Recent, current and upcoming trials at Penn include:
- Developing CAR T-cell therapy: Immune system T-cells attack substances that don’t belong in the body. Adding chimeric antigen receptors (CARs) to T-cells helps the cells better target cancer. A new version at Penn looks for a marker called CDH17. It’s often found in metastasized disease in pancreatic NETs (about 50 percent), gastrointestinal NETs (more than 90 percent) and more common solid tumors. Learn more about CAR-T cell therapy, which Penn first developed for blood cancers.
- Testing a newer targeted therapy type: We joined earlier trials for Welireg (belzutifan), the first therapy of its kind. Those studies led to approval for particular tumors of Von Hippel-Lindau (VHL) syndrome, including some pancreatic NETs. The new trial studies the effect on metastatic pancreatic NETs and pheo-paras in people with and without VHL. It’s one of the few pheo-para trials in the US.
- Verifying PRRT for lung NETs: The leading PRRT agent, Lutathera (lutetium 177 dotatate), is approved for GI and pancreatic NETs. While we can also use it for lung NETs, doctors need more evidence for formal approval. The trial compares Lu 177 to an existing targeted therapy, everolimus.
- Finding optimal liver embolization: Doctors have used this type of liver-directed therapy for NETs for years to treat metastatic disease. But we lack evidence for which form is most effective with the fewest side effects. A global trial led by Penn compares embolization which blocks the tumor blood supply to embolization which adds chemotherapy. Early trial evidence showed that a third type, which slowly released anti-cancer drugs from tiny beads, didn’t add value and was too toxic. National guidelines changed as a result. Learn more about the randomized embolization trial for neuroendocrine metastases to the liver (RETNET).
- Pairing chemotherapy with radioembolization: This Penn-led trial adds two chemotherapy drugs to another form of liver therapy that delivers targeted radiation with tiny beads. The chemotherapy combination, capecitabine and temozolomide (CapTem), is newer and often less burdensome. It also makes cancer more sensitive to radiation. We believe this approach may benefit people with more aggressive tumors and disease that’s spread to the liver and beyond. Learn more about CapTem plus radioembolization for NET liver metastases.
- Combining targeted therapy with immunotherapy: Targeted therapy doesn’t work as often as we’d like with NETs. This trial combines a newer drug, surufatinib, with immunotherapy for NETs in the lungs, pancreas and gastrointestinal (GI) tract. The immunotherapy, tislelizumab, releases the immune system so it can destroy cancer. Learn more about surufatinib in combination with tislelizumab in subjects with advanced solid tumors.
- Harnessing T-cells: A new drug called tidutamab aims to connect T-cells to the special hormone receptors found in many NETs. Our study looked at advanced NETs in the pancreas, lung and GI tract.
- Delivering precise chemotherapy: The molecule PEN-221 can potentially deliver a special kind of chemotherapy straight to NET cells, using their hormone receptors.
Looking Toward Future Trials
We’re always looking to add promising trials that complement our existing efforts. Ideas we have discussed and may pursue include:
- Combining immunotherapy with ablation, an existing liver therapy that stimulates the immune system as a side effect
- Determining how tumor size affects response to PRRT, CapTem chemotherapy and liver therapy — and how supplemental treatment beforehand can help PRRT succeed
- Trying PRRT for pheo-para
Driving Neuroendocrine Tumor Research at Penn
Improving NET treatment and developing further personalized therapy depend on a better understanding of how tumors form, grow and spread. Our program works on the research that makes clinical trials possible, with a focus on moving insights from the lab to clinical care.
These efforts include taking an innovative look at disease, sharing work through leading publications, and managing a series of unique resources and projects.
Making a Difference: Supporting the NET Biobank and Data Repository
Many of the people who trust us for care also contribute to the NET Biobank and Data Repository. This vital resource contains one of the world’s largest collections of biological samples and medical information related to neuroendocrine tumors.
Anyone with a pheochromocytoma, paraganglioma, or GI or pancreatic NET can volunteer. People whose genetics increase NET risk can also join, even if healthy. Participation involves a few easy steps, none of which affect your treatment:
- Our team collects key information about the tumor and your health, which goes into a registry. One part of the program handles pheo-paras, the other, pancreatic and GI NETs.
- We take a blood sample, if you’re willing.
- If you’re undergoing surgery to remove a tumor, we ask for a tissue sample, if possible.
- Biological samples go into special storage.
- Names and other identifying details get removed from all records and samples.
More than 400 people have participated for pheo-para, and nearly 500 for GI and pancreatic NETs. We share resources with NET researchers around the world and also conduct our own investigations. While you may not directly benefit from those insights, others can. Our research efforts include:
- Learning more about tumor biology
- Finding better ways to predict which tumors are more likely to metastasize and which ones may return
- Identifying new treatment targets
- Improving care in our clinics
- Managing tumors for women who are pregnant
- Developing individualized screening and monitoring for people with genetic risk
- Determining how likely particular, inherited genetic changes are to cause disease
- Studying why some people with genetic risk develop tumors and others don’t
Awarding NET Pilot Funding
We regularly award startup NET research funding across Penn Medicine, not just within our program. These NET program pilot awards have led to projects such as:
- Potentially using drugs called PARP inhibitors to stop cancerous cells from repairing themselves, making them more likely to die
- Possibly tapping CRISPR to delete aspects of tumor cells, creating vulnerabilities for targeting
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