Clinical Trial Opens for Patients with High-Grade Neuroendocrine Cancer
Article Summary
- High-grade neuroendocrine tumors are highly aggressive and new treatment options are badly needed.
- Sylvester researchers offer a new option in a phase 1 clinical trial.
- The new trial will test the novel combination of immunotherapy paired with a tumor-busting virus.
A clinical trial for patients with high-grade neuroendocrine tumors is now open for enrollment at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.
High-grade neuroendocrine cancer is a complex and aggressive condition that has seen few medical advances, in part because its rarity has subdued research investment. Patients have few options beyond conventional chemotherapy.
The new trial offers a fresh approach. Patients will receive a combination of immunotherapy drugs and a tumor-busting “oncolytic” virus injected directly into the tumors.
“We are getting the message across to patients and oncologists, in our region and beyond, that there is now an exciting study for this rare disease,” said Aman Chauhan, M.D., leader of the Neuroendocrine Tumor Program at Sylvester and a Miller School assistant professor in the Division of Medical Oncology, who heads the new trial.
Tumors In Any Organ, at Any Age
Neuroendocrine tumors originate from cells found throughout the body and can affect most organ systems. They most often attack the lungs, gastrointestinal tract, gynecological tract and prostate.
About one-sixth of neuroendocrine tumors are classified by pathologists as high grade. Survival rates from high-grade cancer vary with the site of disease, but most patients succumb within a year or two, said Dr. Chauhan. People older than 60 account for thaemajority of cases, but these aggressive tumors can strike people of any age.
Victims of high-grade disease include Sean Stone, an emerging Hollywood producer who passed away last March at only 26 years of age, and Nichole Borchard, a vibrant mother of two young children who died in September 2024 at age 39. Her family established the Nichole Borchard Foundation to honor the legacy of “an extraordinary woman who fought like hell to live and get better.” And Stone’s family founded the Sean Stone’s Neuroendocrine Carcinoma Fundraiser, which supports research at Sylvester.
In his previous role as an oncologist at University of Kentucky Markey Cancer Center, Dr. Chauhan treated a young man with high-grade disease, Austin Foley.
“He was a very sweet person and the reason I got into this field,” said Dr. Chauhan, whose care helped Foley fulfill his wish to see Ireland with his family before he passed away. “We found treatments to keep him alive and make him feel better so he could make this dream trip.”
Despite his physicians’ best efforts, Foley died at age 27, within two years of his diagnosis.
“That is where my research journey started,” said Dr. Chauhan.
Checkpoint Inhibitors and “Hot” Tumors
In the new trial, Dr. Chauhan will combine immunotherapy drugs called checkpoint inhibitors with SVV-001 (Seneca Valley Virus-001), an oncolytic virus that has been tested for safety in previous trials.
Checkpoint inhibitors have broadened treatment options for a growing list of tumor types, from melanoma to lung cancer.
Very few high-grade neuroendocrine carcinomas respond to the drugs. But when they do, the effect is often long lasting.
“When it works, it works like a charm,” said Dr. Chauhan.
The challenge is to increase the number of patients who fully respond to immunotherapy.
That’s where Seneca Valley Virus comes in. SVV doesn’t infect normal cells. It grows inside tumor cells and busts them open. When the tumor cells burst, they release their contents, activating the immune system. The virus then goes on to infect other tumors and keeps the chain reaction going.
The checkpoint inhibitors in turn amp up the immune response against tumor components. In the trial, patients will receive the checkpoint inhibitors nivolumab and ipilimumab.
Dr. Chauhan and his colleagues previously tested the approach in preclinical cancer models. Tumors shrank and yielded durable responses, he said.
In those studies, the oncolytic virus turned immune “cold” tumors into “hot” tumors that respond to checkpoint inhibitors. The drugs in turn acted like “fuel to the fire,” strengthening the attack against the tumor, said Dr. Chauhan.
Biomarker Boost
The new phase 1 trial will enroll about 36 people whose tumors have become resistant to or failed previous lines of therapy.
“These are patients who don’t have any other options left. They have exhausted all standard approaches,” said Dr. Chauhan.
The aim is to find safe combination doses and to begin comparing effectiveness with historical data from standard-of-care treatment.
Patient tumors will also be tested for the presence of a new biomarker found on tumor cells called TEM8, which binds to the oncolytic virus. This phenomenon is unique to SVV and allows the virus to attach to cancer cells and infect them effectively. TEM-8 makes SVV a targeted immunotherapy drug.
Partners in Research and Care
In the past two years, more than 550 new patients from 30 different states and 10 different countries have come to Sylvester for treatment and access to neuroendocrine cancer clinical trials.
Dr. Chauhan heads several clinical trials for neuroendocrine tumors and carcinomas. This is his first investigator-initiated trial at Sylvester dedicated to high-grade neuroendocrine disease.
“Sylvester invested in this. They brought me in and gave me a free hand to open the trials we needed and hire the people to build this together,” said Dr. Chauhan, who joined Sylvester in 2023.
Dr. Chauhan credits patient advocacy groups with helping to get the word out and contributing to clinical trial enrollment. These include organizations such as the Minkahz NETs Mission, Neuroendocrine Cancer Foundation, the Neuroendocrine Cancer Awareness Network, the Healing NET Foundation and the Neuroendocrine Tumor Research Foundation.
“Dr. Chauhan is just passionate and compassionate, and he has the drive,” said Susan Meckler Plummer, the founder of Minkahz NETs Mission.
Plummer founded NETs Mission after her husband, Larry Sylvan, died at age 61 from the condition. She also launched a Facebook support group for patients with high-grade neuroendocrine cancer, which meets online monthly with Dr. Chauhan.
“One of the last things Larry said to me was, ‘Please don’t let anybody do this alone like we had to,’” said Plummer.
Dr. Chauhan and his colleagues continue to make sure that doesn’t happen to new patients, as the team develops fresh research ideas to bring to the clinic.
“This is just the start,” Dr. Chauhan said.
Tags: cancer research, clinical trials, Dr. Aman Chauhan, neuroendocrine cancer, Neuroendocrine Tumor Program, Sylvester Comprehensive Cancer Center