For years researchers have been working to develop systems to avert the systemic toxicities that chemotherapy produces when treating cancer patients. Limiting dosages means more patients are lost to disease.

Now, Delcath Systems (New York) has reached Phase III trials with its technology that facilitates ultra-high dose delivery of chemotherapy directly to the liver to treat liver cancer.

The Delcath System (DS) uses a minimally invasive procedure combined with a catheter technology to isolate the blood flow from the liver, allowing for the infusion of a bolus dose of chemotherapy while preventing systemic toxicities. The procedure is being tested at the U.S. National Cancer Institute in a Phase III trial for metastatic melanoma to the liver from ocular and cutaneous origin.

Delcath also has a Phase II trial for metastatic neuroendocrine tumors and adenocarcinomas to the liver, as well as primary liver cancer.

Both trials are using a 3 mg/kg dose of melphalan directly to the liver. and both are showing impressive and durable tumor responses, according to the company. Previous testing used a variety of drug agents, including doxorubicin and 5FU. Data generated from the Phase III pivotal trial will serve as the basis for seeking final FDA approval under a Special Protocol Assessment.

“We all know that systemic chemotherapy poisons the whole body,” Richard Taney, president/CEO of Delcath, told Medical Device Daily. “The DS is regional cancer treatment. It isolates an organ of the body and treats it with chemotherapy and then goes one step beyond by filtering the blood and returning it to the liver.”

The main component of the DS is a 16 Fr double balloon catheter inserted via the femoral vein and positioned within the retrohepatic inferior vena cava to isolate the hepatic venous outflow. Two independently-inflated low-pressure occlusion balloons are positioned to block the inferior vena cava above and below the hepatic venous outflow. When the balloons are inflated, isolating the venous outflow, fenestrations on the catheter allow the hepatic venous blood to exit through the catheter into an extracorporeal blood circuit.

Blood which exits from the proximal end of the catheter is pumped through two carbon filters before returning to the systemic circulation through the internal jugular vein.

Patients in the trials usually receive the treatment at four-week intervals and up to 10 treatments have been administered to a patient.

“We can administer chemotherapeutics over 30 minutes, and then we capture the blood exiting the liver — heavily doused with chemotherapeutics — run it through a filtration systems like a heart bypass, then return the cleansed blood,” Taney said.

“The process is over in an hour. The pump is turned off, catheters are withdrawn. This can be administered once every 21 days. It’s a repeatable therapy.”

So far in the phase III trial, researchers are reporting 30% to 100% reduction in tumor volume and 50% response in patients.

“Our target patients have at least 20 tumors – a heavy tumor load – which would typically be treated by surgical resection,” Taney said. “We are the only technology out there that can bathe the entire organ in chemotherapeutics. A patient receiving chemotherapy systemically would typically get .4 mg/kg of body weight. We can deliver a targeted regionalized does of 3 mg/kg.

“We’re not simply stabilizing the disease, we are seeing dramatic reduction in tumor size if not complete responses,” he added. “The gold standard in liver cancer is to cut it out. Ninety percent of cases are non-resectable. We can reduce tumor load and make non-resectable cases resectable.”

While the company doesn’t claim to be curing cancer with its DS, Taney said that, unlike surgically isolated hepatic perfusion (IHP) which can be performed only once, this procedure (percutaneous hepatic perfusion) can be administered repeatedly over an extended period, thus improving its life-saving potential.

“When people die of melanoma, they are dying of metastatic disease,” he said. “But usually when it goes to the liver, it’s a death sentence. We had a patient who had over 50% replacement of her liver with tumors. We cured her liver cancer, but she died 42 months later of brain cancer.”

Delcath has filed the DS as a class III medical device, not a 510(k) because there is no predecessor device. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of health, or which present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with class III devices, general and special controls alone are insufficient to assure the safety and effectiveness of these kinds of devices. Therefore, DS will require the more stringent premarket approval application route.

Taney added that Delcath also has an investigational new drug application in the works because, even though they are working with FDA-approved chemotherapeutics, the dosages are extremely high.

The DS is Delcath’s only product, and Taney points out that its potential applications for other diseases are broad. “Basically any drugs that have failed because of high systemic toxicity may be a candidate for DS,” he said.

The company has enough funding for the immediate future, $19 million with a monthly burn of $500,000 and no outstanding debt.

The DS is comprised of parts that come from Medtronic (Minneapolis) and B. Braun (Bethlehem, Pennsylvania). Nothing is manufactured by Delcath.

If approved, the DS may be marketed independently, Delcath estimating that the DS kits would cost $5,000 apiece and that his company could garner $15 million if it could penetrate even just 1% of the potential market. Global sales could multiply that number by 10.

Given the positive responses to date, Delcath has added a fourth arm to its Phase III trial targeting metastatic melanoma to treat patients who have recurrence of disease. Patients in that arm started treatment last June and, so far, have had 100% positive responses.