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Drug shows safety, efficacy for precancerous stomach lesions

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An early-stage clinical trial, supported by the Department of Defense, has demonstrated that the targeted cancer drug trametinib shows potential as an interventional therapy to reprogram precancerous gastric lesions, potentially preventing them from becoming malignant, and that it can be administered safely.

The results of the Phase 1 trial involving 15 patients, which were published recently in Gastroenterology, were pleasantly surprising, said James Goldenring, MD, PhD, professor of Surgery and of Cell and Developmental Biology at Vanderbilt University Medical Center.

The primary goal of this trial was to evaluate whether a low-dose, limited duration treatment of two weeks with trametinib would be safe for patients at risk for developing a second cancer after having undergone resection of a Stage 1 gastric cancer. The drug also showed promise that it could be the first therapeutic intervention against precancerous lesions in the stomach.

Endoscopies revealed that trametinib reversed metaplasia, which is an abnormal change of cells into ones that are non-native to the tissue and can progress to dysplasia, an irreversible change in cell development that can lead to cancer. While the 15 patients in the study had no evidence of recurrent cancer, they did have extensive metaplasia when they entered the study.

“I was pleasantly surprised at how much benefit we could see in the endoscopies after one month and one year; it really was pretty remarkable,” said Goldenring, the Paul W. Sanger Professor of Experimental Surgery.

The reversal of the metaplasia could be viewed in endoscopic images and was confirmed with biopsies.

“I think that’s almost more compelling than anything else in this study,” Goldenring said. “I honestly did not expect endoscopies to be that different, but they were.”

However, he noted that follow-up clinical trials with more participants are needed to further validate the drug’s efficacy. The only significant side effect among the participants was one patient with a mild increase in blood pressure after trametinib treatment that returned to normal after the patient stopped taking the drug.

The patients in the study were recruited from Japan, where the clinical trial was led by Sachiyo Nomura, MD, PhD, in collaboration with Goldenring. Trametinib is an inhibitor of the MEK signaling pathway. MEK, an abbreviation for the mitogen-activated extracellular signal-regulated kinase pathway, plays an integral role in the development of stomach cancer.

The study was supported by a $2.5 million Department of Defense Translational Team Science Award, which is also supporting another clinical trial in the United States with similar aims. The U.S. clinical trial will evaluate the effectiveness of pyrvinium, an existing medicine that has been used for the past 70 years to treat pinworms in children, for a new purpose — reversing metaplasia of stomach cells and killing dysplastic precancerous cells. Pyrvinium also blocks the MEK pathway.

While stomach cancer is one of the three leading causes of cancer-related deaths worldwide, its incidence is lower is the U.S. Nevertheless, it does occur more frequently among minority ethnic groups, and incidence has been rising among young women. DOD support for clinical trials reflects the increased incidence of stomach cancer in minority groups, which make up a higher percentage of the U.S. armed services than of the general population. In the U.S., most stomach cancers are diagnosed at late stages when they are more difficult to treat.

Goldenring said he hopes the MEK inhibitor study will spur more research into therapeutic interventions for people with precancerous lesions who are at high risk for cancer.

“I’m hoping that this is a direction that multiple researchers might take in the future to really change the dynamics of how we’re going to intervene so that people don’t develop cancer,” he said. “That’s a different mindset than we’ve had previously.”

Eunyoung Choi, PhD, associate professor of Surgery and of Cell and Developmental Biology, is a co-principal investigator of the pyrvinium study along with Katherine Garman, MD, associate professor of Medicine at Duke University. Choi is also a co-author of the study published in Gastroenterology.

Goldenring is supported by grants from the Department of Defense, a Department of Veterans Affairs Merit Review Award, and the National Institutes of Health (R01DK101332 and R01CA272687. Choi is supported by grants from the National Institutes of Health (R37CA244970 and R01CA272687), the Department of Defense, the American Association for Cancer Research, and an American Gastroenterological Association Robert & Sally Funderburg Research Award.

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This phase I/II trial studies the side effects and best dose of temozolomide and M1774 and how well they works in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and may have spread to nearby tissue, lymph nodes, or distant parts of the body (advanced). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. M1774 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Adding M1774 to temozolomide may shrink or stabilize cancer for longer than temozolomide alone.
Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine change in disease symptoms of etentamig compared to standard available therapies in adult participants with relapsed/refractory (R/R) MM. Etentamig is an investigational drug being developed for the treatment of R/R MM. This study is broken into 2 Arms; Arm A and Arm B. In Arm A, participants will receive etentamig as a monotherapy. In Arm B, participants will receive the standard available therapy (SAT) identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable. Around 380 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 140 sites across the world. In Arm A participants will receive etentamig as an infusion into the vein in 28 day cycles, during the 3.5 year study duration. In Arm B, participants will receive the SAT identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable, during the 3.5 year study duration. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
The purpose of this research study is to see if loncastuximab tesirine has any benefits at dose levels researchers found acceptable in earlier studies in patients with related forms of immune cell cancers. The researchers want to find out the effects (good and bad) that loncastuximab tesirine has on the participant and the participant's condition.

The real MVP: Fitness challenge raises funds in honor of 4-year-old cancer patient

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When 4-year-old Monroe Peterson was diagnosed with cancer, her family was determined to not only rally around her in support but also wanted to make a difference for other patients and families going through a similar experience.

To honor her journey, in November 2024 Monroe’s father, fitness expert and celebrity trainer Gunnar Peterson, started the MVP Challenge on his app, Common Ground, to raise awareness and funds for pediatric cancer efforts at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

The MVP Challenge, named for Monroe Vivian Peterson, included four weeks of guided workouts, question and answer sessions with Gunnar, and an opportunity to win special prizes. The fitness challenge raised funds to support pediatric cancer research, training and care at Monroe Carell.

“For months, Monroe has faced this battle with more grit, determination and positivity than I’ve ever seen,” said Peterson. “She hasn’t backed down; she doesn’t quit; and she moves forward with a smile on her face every day. To honor her strength, we launched the MVP Challenge as a way to come together as a community, push ourselves and raise funds to support children’s cancer treatment and research.”

Monroe Peterson with her mother, Jessica, left, and Debra Friedman, MD, MS.
Monroe Peterson with her mother, Jessica, left, and Debra Friedman, MD, MS.

Monroe was diagnosed with acute myeloid leukemia and completed two rounds of chemotherapy. She received two bone marrow transplants, one from each of her older brothers, and she is now in remission.

During her treatment, Monroe’s family says that she brought positivity, joy and levity to those around her and earned the nickname MVP. Many family members, friends and community members came together in support of the challenge to make it a success.

“We are blown away by the incredible success of the MVP Challenge and know that it would not have been possible without the advocacy, outreach and community engagement work of Gunnar, Jess and the whole Peterson family,” said Debra Friedman, MD, MS, director of the Division of Pediatric Hematology and Oncology at Monroe Carell, deputy director of Vanderbilt-Ingram Cancer Center, and holder of the E. Bronson Ingram Chair in Pediatric Oncology. “This challenge was a wonderful way to honor Monroe’s journey and tenacious spirit.”

Funds raised from the MVP Challenge will support Monroe Carell’s vision to advance personalized pediatric, adolescent and young adult cancer care in the region, specifically leukemia and stem cell research.

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The main purpose of this study is to assess the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who have not progressed after receiving definitive concurrent chemoradiotherapy (cCRT).

Triptorelin for the Prevention of Ovarian Damage in Adolescents and Young Adults With Cancer

This phase III trial compares the effect of giving triptorelin vs no triptorelin in preventing ovarian damage in adolescents and young adults (AYAs) with cancer receiving chemotherapy with an alkylating agents. Alkylating agents are part of standard chemotherapy, but may cause damage to the ovaries. If the ovaries are not working well or completely shut down, then it will be difficult or impossible to get pregnant in the future. Triptorelin works by blocking certain hormones and causing the ovaries to slow down or pause normal activity. The triptorelin used in this study stays active in the body for 24 weeks or about 6 months after a dose is given. After triptorelin is cleared from the body, the ovaries resume normal activities. Adding triptorelin before the start of chemotherapy treatment may reduce the chances of damage to the ovaries.

Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer

This phase III trial compares the effect of cabozantinib versus combination dabrafenib and trametinib for the treatment of patients with differentiated thyroid cancer that does not respond to treatment (refractory) and which expresses a BRAF V600E mutation. Cabozantinib is in a class of medications called receptor tyrosine kinase inhibitors. It binds to and blocks the action of several enzymes which are often over-expressed in a variety of tumor cell types. This may help stop or slow the growth of tumor cells and blood vessels the tumor needs to survive. Dabrafenib is an enzyme inhibitor that binds to and inhibits the activity of a protein called B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. Trametinib is also an enzyme inhibitor. It binds to and inhibits the activity of proteins called MEK 1 and 2, which play a key role in activating pathways that regulate cell growth. This may inhibit the growth of tumor cells mediated by these pathways. The usual approach for patients with thyroid cancer is targeted therapy with dabrafenib and trametinib. This trial may help researchers decide which treatment option (cabozantinib alone or dabrafenib in combination with trametinib) is safer and/or more effective in treating patients with refractory BRAF V600E-mutated differentiated thyroid cancer.

Presurgery consults with patients using 3D models improve shared decision-making and reduce anxiety 

Aimal Khan, MD, assistant professor of Surgery at Vanderbilt University Medical Center, noticed the puzzled or anxious expressions of patients trying to fully comprehend what he was saying during preoperative consultations, so he devised visual aids — three-dimensional models of the lower digestive tract. 

The 3D models allowed patients to easily distinguish the ascending colon from the sigmoid colon, along with other parts of the digestive system. Patients could actually see where the surgery would occur, and Khan noticed that they asked more questions, felt more confident and seemed less anxious.  He devised a study to determine whether his personal observations were scientifically valid. 

The study, which was published June 3 in JAMA Network Open, determined that the 3D models made patients feel they played a bigger role in decision-making and that their anxiety levels decreased. 

The patients were scheduled for partial or complete colon and/or rectal resections for colorectal cancer, diverticulitis or inflammatory disease. Fifty-one patients participated in the study with 28 receiving consultations using the 3D models and 23 receiving conventional consultations. The patients in the 3D arm of the study reported a significantly higher involvement in shared decision-making and significantly reduced anxiety levels compared to the other patients. 

Khan and five other Vanderbilt surgeons conducted the study from March 2022 to June 2023.  

“Using 3D models during consultations allowed our patients to truly visualize their surgery, which not only empowered them to take an active role in decision-making but also significantly eased their anxiety. This approach has the potential to transform how we communicate complex information to our patients. We are currently working with surgeons from other specialties, including thoracic surgery, ENT and surgical oncology, to validate these findings in a multicenter randomized trial,” Khan said. 

The findings are important because other studies have shown that improvements in shared decision-making are associated with reduced hospital stays, lower health care utilization, improvement in patient-reported health outcomes and fewer emergency department visits.  

The 3D models used in the study were developed in collaboration with the Department of Radiology. The modular designs, which were made with 3D printing, allowed each segment of the colon and rectum to be magnetically detached and reattached. 

To the knowledge of the study’s authors, this is the first randomized clinical trial to compare the effectiveness of a 3D-printed model with usual care on colorectal surgery patients’ involvement in decision-making, anxiety and education. 

Other Vanderbilt researchers who authored the study are Danish Ali, MD, Shannon McChesney, MD, Michael Hopkins, MD, Molly Ford, MD, Roberta Muldoon, MD, Timothy Geiger, MD, MMHC, Alexander Hawkins, MD, MPH, Georgina Sellyn, MA, Hillary Samaras, RN, and Dann Martin, MD, MS.

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Study shows sharp increase in appendix cancer for Generation X and millennials 

Cases of appendiceal cancer tripled for Americans born between 1976 to 1984 and quadrupled for those born between 1981 to 1989, according to a study published June 9 in the Annals of Internal Medicine. 

The study compared chronological data in five-year intervals from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program, using 1941 to 1949 as the baseline. The lead author, Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, said the findings reveal the need for increased awareness about appendiceal cancer from both clinicians and the public as well as more research to determine the reasons for the sharp spike in incidence.  

Andreana Holowatyj, PhD, MSCI

“When you take these alarming rates that we are seeing for appendiceal cancer across generations, together with the fact that 1 in every 3 patients diagnosed with appendiceal cancer is diagnosed under the age of 50, these point to a timely need for everyone to be aware of the signs and symptoms of appendix cancer.

“Albeit cancer of the appendix is rare, it is important for individuals who have these symptoms to see a health care professional. Ruling out the possibility of an appendix cancer diagnosis, or diagnosing it early, is important for this cancer as we continue to learn what factors may be contributing to this worrisome trend,” Holowatyj said.

Symptoms may include abdominal pain, bloating, changes in bowel habits, and loss of appetite. 

Appendiceal cancer is a rare cancer with about 3,000 new cases diagnosed every year in the United States, according to prior studies, but Holowatyj and colleagues took a closer look at statistics by combing through the SEER database. 

“As incidence rates in younger generations are often indicative of future disease burden, these results support the need for histology-specific investigations of appendiceal adenocarcinoma, as well as increased education and awareness of appendiceal adenocarcinomas among health care providers and the public,” the study stated. 

Appendiceal cancer has had no standardized screening guidelines, risk factors or tumor classifications — a lack of clinical evidence that has resulted in late diagnosis and poor prognosis. Up to 1 of every 2 patients is diagnosed with distant metastatic disease, and five-year survival rates vary between 10% and 63%.  

Earlier this year, Holowatyj and a team of experts identified six key research priority areas to deliver a fundamental understanding of appendiceal tumors and to improve treatments and outcomes for patients.  

The recommendations published Feb. 20 in Nature Reviews Cancer are the result of a concerted focus by the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation to better understand the disease that afflicts an estimated 3,000 new patients across all age groups each year. 

The recommendations arose from the inaugural ACPMP Research Foundation Scientific Think Tank, sponsored by ACPMP and chaired by Holowatyj at Vanderbilt-Ingram Cancer Center in December 2023. 

The current study in the Annals of Internal Medicine received support from ACPMP and the National Institutes of Health (grants K12HD043483 and P50CA236733). 

Other authors on the study are Mary Kay Washington, MD, PhD, professor of Pathology, Microbiology and Immunology at VUMC, Richard Goldberg, MD, of the West Virginia University School of Medicine, and Caitlin Murphy, PhD, MPH, of the UT Health Houston School of Public Health. 

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