Intraperitoneal Therapy Seeks to Address “Nihilism” Around Peritoneal Mets

In an interview with CancerNetwork®, Mustafa Raoof, MD, MS, assistant professor in the Division of Surgical Oncology in the Department of Surgery, and assistant professor in the Department of Cancer Genetics and Epigenetics City of Hope Cancer Center, discussed the basis for conducting a phase 1 dose-escalation trial (NCT04329494) evaluating Mitomycin C pressurized intraperitoneal aerosolized chemotherapy (PIPAC-MMC) in combination with systemic chemotherapy in patients with appendiceal and colorectal carcinomatosis which was presented at the Society of Surgical Oncology (SSO) 2025 Annual Meeting.

Raoof began by providing background regarding the state of peritoneal metastases, explaining that they are historically associated with limited survival, blockages in the intestines and ureters, as well as fluid build-up. Additionally, he expressed that a “nihilism” surrounds peritoneal metastases, given low consideration for clinical trials and having the worst prognosis within stage IV colon or appendix cancers.

He further explained that the trial sought to deliver intraperitoneal therapy following a previously observed failure of intravenous treatments to reach these tumors. Raoof then outlined a novel method his practice has implemented, which includes performing a laparoscopy every 6 weeks and administering aerosol treatment following small incision surgery, to deliver minimally invasive treatment directly to these tumors.

Additionally, the trial assessed the combination of the novel intraperitoneal therapy with PIPAC-MMC and standard systemic therapy in a regimen that was given every 6 weeks for 3 cycles across 4 dose levels. He concluded by explaining that the phase 1 trial was primarily assessing the safety of the combination in patients with peritoneal metastases and was also assessing multiple secondary efficacy end points.

Safety results from the phase 1 trial revealed that the highest toxicity grade was 1/2 in 58% of patients treated with the combination therapy and grade 3 or higher among 31% of patients. A total of 67%, 87%, and 25% of patients receiving 7 mg/m², 12.5 mg/m², and 19 mg/m² of PIPAC-MMC experienced the highest toxicity grade of 1 or 2, and 0%, 12%, and 62%, respectively, experienced grade 3 or higher toxicities.

Transcript:

This was a phase 1 clinical trial of patients who have metastases to the peritoneum from colon cancer or appendix cancer. The peritoneum is an organ in the abdomen that lines the abdominal cavity. Metastases to this [area] are notorious because patients have limited survival and they cause a lot of symptoms in terms of intestinal blockage, blockage of the ureters, [and] ascites or buildup of fluid. Usually, patients have limited options once they develop peritoneal metastases because they are not considered clinical trial candidates. There is a lot of nihilism around peritoneal metastases because, within stage IV colon cancer or appendix cancer, peritoneal metastases have the worst prognosis.

The idea of the trial was to deliver therapy directly in the abdominal cavity. This is borne out from observations that when therapy is given intravenously, which is the majority of systemic therapy, it does not reach the peritoneal tumors. We have been using this novel method that was developed in Europe to deliver therapy in the abdominal cavity in a minimally invasive way. We [perform a] laparoscopy every 6 weeks. Through small incision surgery, we can then give this aerosol treatment directly to the abdomen. I look at it as an optimized way to deliver intraperitoneal therapy.

What we have done is combined the standard systemic therapy in addition to the intraperitoneal therapy. Patients get this treatment every 6 weeks for 3 [cycles]. The purpose of the trial was to see if this approach is safe or not and essentially figure out what dose of the drug we are using is safe. The drug that we are using is called mitomycin C. Patients started with low-dose––dose level 1 and escalated up 4 dose levels. We made it up to dose level 3 so far [in the trial]. The idea was to look at safety, and then the secondary [end points were] to look at efficacy signals to see if patients were benefiting from it.

Reference

Raoof M. Dose escalation phase 1 trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for unresectable appendiceal and colorectal carcinomatosis. Presented at the Society of Surgical Oncology (SSO) 2025 Annual Meeting; March 27-29, 2025; Tampa, FL.