A Novel Dual-Balloon Catheter for the Treatment of Locally Advanced Pancreatic Cancer

IO Learning invited Dr Gandhi to discuss his 2020 Society of Interventional Radiology (SIR) abstract, “Overcoming Limitations in the Treatment of Locally Advanced Pancreatic Cancer With Transarterial Microperfusion Utilizing a Novel Dual-Balloon Catheter.”¹ The accompanying video, available below, offers highlights from the discussion, as well as a walkthrough of the RenovoCath dual-balloon catheter (RenovoRx, Inc.).²

I’m an interventional radiologist and interventional oncologist at the Miami Cardiac & Vascular Institute and the Miami Cancer Institute, part of Baptist Health South Florida. I am going to discuss pancreatic cancer and challenges in the treatment of pancreatic cancer, as well as research we’re doing that may advance the treatment of pancreatic cancer. Pancreatic cancer is the third leading cause of cancer deaths in the United States and is probably going to become the second leading cause in the coming years. More than 55,000 new cases are diagnosed in the United States each year, and over 300,000 new cases are diagnosed per year worldwide. So it certainly has a very high fatality rate and is one of the most deadly cancers.

My focus in this discussion is specifically in regard to patients with locally advanced pancreatic cancer (LAPC). These are patients who have unresectable disease secondary to vascular involvement — typically, greater than 180° involvement of the superior mesenteric artery or the celiac axis as well as superior mesenteric vein or portal vein obstruction that is not amenable to reconstruction. Systemic chemotherapy is the standard of care for the treatment of patients with LAPC. Many of these patients are treated in a similar fashion to patients with metastatic disease, and systemic chemotherapy is the best treatment currently available. Standard chemotherapy for LAPC includes gemcitabine and nab-paclitaxel (also known as Abraxane; Bristol-Myers Squibb). Some can be treated with FOLFIRINOX as well, although that treatment tends to be associated with greater toxicity.

One of the main issues of standard-of-care systemic chemotherapy is that there is limited drug penetration into the actual pancreatic cancer. As a result, the intended chemotherapy is not getting into the actual pancreatic cancer to the degree that we would like. In addition, there are systemic side effects and toxicity related to non-localized therapy. Local control appears to be important for the survival of patients with LAPC. Therefore, we are examining the utility of a proprietary catheter known as the RenovoCath (RenovoRx). It is a double-balloon occlusion catheter that is utilized to deliver targeted chemotherapy directly to the LAPC. The goal is to isolate the vessels surrounding the pancreatic cancer and to deliver high-dose chemotherapy directly to the cancer, ideally increasing survival and slowing the progression of disease in these patients, who have very limited options. 

A phase I dose-escalation study was published in the Journal of Pancreatic Cancer in 2017.³ Historical controls in patients with LAPC demonstrate a median overall survival of around 12 to 14 months. However, the phase I RenovoCath study demonstrated a median overall survival of about 27.5 months. These results led to the creation of the TIGeR-PaC study,  a phase III, multicenter, randomized clinical trial that compares systemic chemotherapy with intra-arterial delivery of systemic chemotherapy via the RenovoCath in patients with LAPC. The primary objective is overall survival from the time of randomization. Patients will be evaluated from multiple secondary objectives as well, including progression-free survival, objective response rate, duration of response, quality of life, toxicity and tolerability, and safety. Inclusion criteria include histologically confirmed pancreatic adenocarcinoma with the initial diagnosis within 6 weeks and patients must have unresectable LAPC, as defined by the NCCN guidelines. The goal is to enroll a total of 320 patients; at this point, 77 patients have been enrolled at a total of 28 sites both within the United States and internationally, and we are one of the trial sites for this randomized clinical trial.

The trial is designed so that the patients initially get standard of care systemic chemotherapy and then a follow-up scan to ensure that there is no disease progression. Provided there is no disease progression, the patients then get radiation as well, followed by another follow-up scan. Only patients who have not progressed at that point in time are subsequently randomized to either systemic  chemotherapy alone or gemcitabine delivery via intra-arterial double-occlusion balloon Renovo catheter. Patients are treated with a total of 8 treatments (4 cycles of intra-arterial therapy given every 2 weeks). 

In summary, this phase III trial is ongoing, and it will take some time to get these results, but localized intra-arterial delivery of chemotherapy (specifically, gemcitabine) utilizing the RenovoCath clearly demonstrates encouraging results in stabilizing local disease in the early studies. This benefit was particularly evident in patients who had prior induction therapy with radiation, so that is included within this clinical trial. The RenovoCath is a very promising technology. The hope is that this phase III, multicenter, randomized clinical trial will provide definitive evidence as to whether this therapy can improve survival in these patients with this very deadly disease.

References

1. Manchec B, Gandhi R. SIR abstract poster #959. Available at https://www.sirmeeting.org. Accessed on 2020 June 8.

2. RenovoCath® device product information and specifications. Available at https://renovorx.com/. Accessed on 2020 June 8.

3. Rosemurgy AS, Ross SB, Vitulli PL, Malek R, Li J, Agah R. Safety study of targeted and localized intra-arterial delivery of gemcitabine in patients with locally advanced pancreatic adenocarcinoma. J Pancreat Cancer. 2017;3:58-65.

Address for Correspondence: Ripal T. Gandhi, MD, FSIR, FSVM, Miami Cardiac and Vascular Institute, Miami Cancer Institute, Miami Vascular Specialists, 8900 North Kendall Drive, Miami, FL 33176. Email: ripgandhi@yahoo.com