By refocusing on multidisciplinary homegrown studies, the Head and Neck Surgery division’s clinical trials program is poised for a dramatic and impactful expansion in the coming months and years.
Devraj Basu, MD, PhD, FACS, is determined to increase the number of clinical trials available to Penn Medicine’s head and neck cancer patients—and he wants the Head and Neck Surgery division to lead them there.
In recent months, he has begun laying the groundwork for this ambitious vision, networking across disciplines and the health system, hiring staff, and developing potential opportunities. He emphasizes the benefit of trial designs integrating contributions from multiple scientific and clinical disciplines and has been working on nurturing the collaborative culture within the head and neck cancer program in anticipation of this expansion.
A head and neck surgeon and cancer biologist, Dr. Basu says that while he wants to increase the number of the division’s clinical trials, he and his colleagues need to be mindful to avoid redundancy as they fill gaps in resources across the institution. He is particularly focusing on multidisciplinary trials that center on therapies in which basic and translational scientists at Penn are already significantly invested. He emphasizes the need for a potential trial to involve multiple interests, and has been working on nurturing the collaborative culture within the head and neck cancer program in anticipation of this expansion.
Dr. Basu recently hired a clinical research coordinator, who’s been helping him procure head and neck cancer specimens for research use. But he envisions her role evolving in the coming months to include the coordination of a new clinical trial. At that point, Dr. Basu will lean on Karthik Rajasekaran, MD, FACS and his extensive experience with clinical trials.
Since joining the division eight years ago, Dr. Rajasekaran, a head and neck oncologic and microvascular reconstructive surgeon, has enthusiastically pursued clinical trials. He says he sees these studies as a means to keep up with the newest advances and technologies in the field.
“You need a well-oiled machine in order to be successful with this because with any clinical trial, there’s a tremendous amount of work that needs to be done in compliance,” Dr. Rajasekaran says. “I’m grateful to work with an exceptionally hardworking and dedicated clinical research team. Their efforts enable me to be my most efficient while pursuing my passion for patient care and contributing to scientific advancement through clinical research.”
Efficiency as a Goal
Penn Medicine also has had an eye toward efficiency. In 2024, a single institutional review board was installed for the entire health system, and the protocol for cooperative group trials was updated. Now, rather than separate implementations for each participating site, there’s one standard implementation for such trials and a single principal investigator.
Dr. Basu believes these ongoing developments are decreasing barriers to activating such trials across practice sites, and he expects them to ultimately facilitate the growth and reach of the division’s trials portfolio in the coming years.
National Efforts
While the Head and Neck Surgery division, as of this writing, had yet to realize its first homegrown clinical trial under Dr. Basu, a number of national clinical trials at various stages have engaged its surgeons and scientists, including Dr. Rajasekaran, who is participating in a phase III clinical trial that’s assessing the safety and efficacy of an experimental drug called ALM-488. This drug features a compound that attaches to and illuminates the intricate network of nerves in the head and neck, enabling surgeons, in theory, to better preserve them during complex operations.
Last fall, radiation oncologist J. Nicholas Lukens, MD, presented the results from the TORS 2.0 trial (NCT03729518) at the 2024 American Society for Radiation Oncology Annual Meeting. According to Dr. Basu, the trial “reflects our longstanding efforts to reduce doses and fields of adjuvant radiation after surgery for human papillomavirus-related oropharyngeal squamous cell carcinomas.
The TORS 3.0 trial (NCT03729518), the follow-up to TORS 2.0, is testing postoperative radiation dose reductions as low as 30 gray in a cohort of carefully selected patients. Dr. Basu says it is “achieving its enrollment targets.” Alexander Lin, MD, is the principal investigator.
HPV+ Head and Neck Cancer Translational Center of Excellence
Dr. Basu recently established the HPV+ Head and Neck Cancer Translational Center of Excellence at the Abramson Cancer Center, through which he and a team of surgeons and scientists are developing multiple trials that, in his words, “seek to leverage new classes of DNA damage response inhibitors that can potentially improve cancer control by both direct and immune-mediated effects on HPV-related cancer cells.”
These therapeutics, he adds, will be tested in both recurrent/metastatic patients and in the preoperative window for HPV-related tumors at high risk of recurrence. In the latter's case, the therapeutics will be combined with conventional immunotherapy and limited radiation doses to metastatic lymph nodes.
Separately, a phase I trial that will start enrolling in February 2025 is focused is focused on mitigating the durable toxicities of head and neck cancer therapy. Here, a novel gene therapy vector will be delivered into the parotid duct in an effort to increase saliva production in patients with chronic radiation-induced dry mouth symptoms. The principal investigator is Christopher H. Rassekh, MD.
Dr. Basu says the division has entered the “very active” field of window of opportunity trials—a type of clinical trial where cancer patients receive an experimental treatment during the short period of time between their diagnosis and the start of their standard cancer treatment—as well as neoadjuvant trials, wherein patients receive cancer treatment before surgery to shrink their tumor.
These trials require close multidisciplinary collaboration, Dr. Basu adds.
“Neoadjuvant anti-PD1 immunotherapy is rapidly advancing toward standard use for advanced HPV-negative head and neck cancers,” he says. “Our efforts to build upon this emerging standard are reflected in a window of opportunity trial that’s studying the effect of adding a CD40 agonist antibody, an activator of tumor antigen presentation, to anti-PD1 therapy.” Entitled CD40 Agonist and PD-1 Inhibitor in HNSCC (NCT06159621), Lova Sun, MD, MSCE, is the principal investigator.
Multiple other window of opportunity and neoadjuvant trials are in the planning and regulatory approval stages, according to Dr. Basu, including one that will explore novel anti-tumor effects of lidocaine, which, he says, has shown agonist activity at T2R bitter taste receptors expressed on HPV-related oropharyngeal cancers. Ryan Carey, MD, will be the principal investigator.