Sylvester Duo Advances Research on Aggressive, Rare Gynecologic Cancers
Article Summary
- Dr. Aman Chauhan and Dr. Abdulrahman Sinno are testing a novel combination of treatments for patients with neuroendocrine cancers who haven’t responded to conventional cancer therapies.
- These cancers are rare but deadly. Patients with advanced cases often live only a year or so after diagnosis.
- The researchers say Sylvester’s status as an NCI-designated cancer center puts them in a good position to conduct the research.
Aman Chauhan, M.D., an expert on neuroendocrine cancers, and Abdulrahman Sinno, M.D., an expert on gynecological cancers, are collaborating with industry partners to conduct an investigator-initiated, phase 1 clinical trial. The trial will test a novel combination of treatments for patients with gynecological and other types of neuroendocrine cancers who haven’t responded to conventional cancer therapies.
Aggressive and Fast-spreading Cancer
Gynecological neuroendocrine carcinoma (NEC) is rare, occurring in approximately one in 100,000 cases. Also known as high-grade neuroendocrine cancer, it is considered a very aggressive and fast-spreading cancer.
For patients with NEC, current treatment options are extremely limited. Chemotherapies have had a poor success rate.
“When it’s advanced, most patients don’t survive for more than a year, year-and-a-half,” said Dr. Chauhan, an associate professor in the Division of Medical Oncology at the University of Miami Miller School of Medicine. “And a lot of our patients with gynecological neuroendocrine cancer are young patients with families. So, we are really taking up the challenge to try to fight this cancer and the breakthroughs will come through research.”
Theranostics and Neuroendocrine Cancers
As the only National Cancer Institute (NCI)-designated cancer center in South Florida, Sylvester is one of the few academic medical centers with expertise in managing NEC cancers.
“We found a window here where we’re able to leverage the expertise that’s available within our cancer center in theranostics and in other areas that are specific to neuroendocrine cancers to improve outcomes for women with these rare gynecologic malignancies,” said Dr. Sinno, an associate professor in the Division of Gynecological Oncology at the Miller School.
Sylvester is becoming a national and international referral center for neuroendocrine cancers. This visibility is especially important because of the aggressive nature of these cancers.
“This is not something that you can wait and watch. It’s so important for patients to seek an opinion at a specialized center in a timely fashion,” said Dr. Chauhan.
A Mission to Advance Scientific Knowledge
As an academic medical center, Sylvester has an advantage over smaller cancer centers. Its researchers can conduct scientific research on rare cancers through non-industry-sponsored, or investigator-initiated, clinical trials.
For a pharmaceutical company to sponsor a clinical trial, it must promise to be profitable somewhere along the way. So, companies tend to sponsor trials only for the most prevalent cancers.
Universities, on the other hand, have a mission that focuses less on profitability than on the advancement of knowledge.
“There are certain things that we as a university can do that other people cannot, and that’s because we have an academic and scientific mission. We can do things that aren’t financially feasible for other people to do. If it’s something that has scientific merit, we’ll do it,” said Dr. Sinno.
Clinical trials benefit patients as they further cancer research.
“The whole purpose of a clinical trial is that you’re able to offer a patient a drug which otherwise they don’t have access to. And a lot of times, with these rare tumors, this is crucial,” said Dr. Sinno. “The pipeline to get drugs approved takes about 10 to 12 years. It’s not a rapid process. And so, we want patients who come to see us to have access to the latest and greatest today, not in 20 years.”
Industry Partnership
Sylvester is already conducting one industry-sponsored clinical trial for gynecologic NEC cancer treatment. The trial is testing a type of immunotherapy drug known as DLL3 BiTE (for bispecific T-cell engager). The drug was found to be so effective in treating NEC cancer of the lung that, as of May 2024, the FDA approved its use for small-cell lung cancer even before the completion of a phase 3 trial.
However, patients with high-grade neuroendocrine cancer outside the lung still don’t have access to that drug outside of clinical trials.
“I’m very happy to say we are one of the very few centers in the country that has access to that drug trial. So, if you have newly diagnosed gynecological high-grade neuroendocrine cancer, we can consider you for that DLL3 BiTE antibody drug trial,” said Dr. Chauhan.
New Combination Immunotherapy Provides Hope
Beyond the DLL3 BiTE antibody drug trial, Drs. Sinno’s and Chauhan’s investigator-initiated phase 1 clinical trial is about to get off the ground. Dr. Chauhan estimates that in three to four months, it will be open for enrollment.
The trial will test a novel immunotherapy combination for patients with NEC cancers.
In the current standard of care, patients with these rare cancers begin treatment with chemotherapy, then undergo a course of novel immunotherapies. Some patients respond very well to the treatment. But those who don’t need a backup plan.
“The standard treatments, they’re there, but they’re not as exciting, and they don’t lead to a long-lasting effect. So, we are trying to find a drug combination that will hopefully have a longer, durable response, so patients remain cancer-free for much longer and hopefully even get cured,” said Dr. Chauhan.
Patients in the trial will be given conventional immunotherapy drugs to start. Then researchers will introduce an oncolytic virus, a type of virus that infects high-grade neuroendocrine cancer cells.
Regardless of the location of the tumor, researchers believe this therapy will work on NEC cancer. Preclinical data showed what Dr. Chauhan called, “deep, durable responses.”
He said, “We inject the virus directly into the tumor, where it grows and divides and thrives, and then eventually kills the cancer cell, because they literally explode. The virus eats it up from the inside.”
Not only does injecting the virus into the tumor kill the cancer cells, but it also provokes an immune system response. In ordinary circumstances, the body would recognize a tumor as a threat and would take care of it like it does viruses or bacteria. NEC cancers have a way of remaining “invisible” to the immune system, which allows it to grow and thrive. The oncolytic virus essentially makes the tumor “visible,” allowing the immune system to better do its work.
While patients with gynecologic NEC cancers are the focus, since treatment is the same, the trial will also include patients who have the same kind of cancer in other locations in the body.
Sylvester will be the only site in the United States that will have access to this combination of conventional immunotherapy drugs and the novel oncolytic virus drug.
“We’re finally seeing some long-overdue research efforts in this rare subtype, and I’m hopeful that in the future we’ll have better treatments for our patients,” said Dr. Chauhan.
Tags: cancer research, clinical trials, Dr. Abdulrahman K. Sinno, Dr. Aman Chauhan, gynecological oncology, neuroendocrine cancer, Neuroendocrine Tumor Program, rare diseases, Sylvester Comprehensive Cancer Center